A Multiple-ascending-dose Study to Evaluate the Efficacy, Safety, and Pharmacokinetics (PK) of MEDI0382 in Overweight and Obese Participants With Type 2 Diabetes Mellitus
Sponsor
MedImmune LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT02548585
Collaborator
(none)
113
11
7
14.6
10.3
0.7
Study Details
Study Description
Brief Summary
A Phase 1/2, multiple dose study with 6 cohorts of ascending doses designed to evaluate the efficacy, safety and pharmacokinetics (PK) of MEDI0382 in participants with Type 2 Diabetes Mellitus (T2DM).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
This is a randomized, double-blind, placebo controlled study designed to evaluate the efficacy, safety, and PK of MEDI0382 administered as multiple daily SC doses to participants with T2DM. Approximately one hundred and seven participants will be enrolled across 6 cohorts. In cohorts 1-3 the participants will be randomized to MEDI0382 or placebo (2:1). In Cohort 4, participants will be randomized to MEDI0382 or placebo (1:1). In cohort 5 and 6 participants will be randomized to MEDI0382 or placebo (3:1).
Study Design
Study Type:
Interventional
Actual Enrollment
:
113 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2, Randomized, Double-blind, Placebo-controlled, Multiple-ascending-dose Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MEDI0382 in Overweight and Obese Subjects With a History of Type 2 Diabetes Mellitus
Actual Study Start Date
:
Dec 9, 2015
Actual Primary Completion Date
:
Feb 24, 2017
Actual Study Completion Date
:
Feb 24, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Participants will receive placebo (matched to either 100 micrograms [mcg], or 150 mcg or 200 mcg or 300 mcg of MEDI0382) subcutaneously (SC) once daily from Day 1 to Day 7 (Cohort 1); or Day 1 to Day 11 (Cohort 2); or Day 1 to Day 15 (Cohort 3); or Day 1 to Day 41 (Cohort 4); or Day 1 to Day 22 (Cohort 5); or Day 1 to Day 17 (Cohort 6). |
Drug: Placebo
Placebo administered subcutaneously.
|
| Experimental: Cohort 1: MEDI0382 100 mcg Participants will receive MEDI0382 100 mcg SC once daily from Day 1 to Day 7. |
Drug: MEDI0382
MEDI0382 administered subcutaneously.
|
| Experimental: Cohort 2: MEDI0382 150 mcg Participants will receive MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). |
Drug: MEDI0382
MEDI0382 administered subcutaneously.
|
| Experimental: Cohort 3: MEDI0382 200 mcg Participants will receive MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). |
Drug: MEDI0382
MEDI0382 administered subcutaneously.
|
| Experimental: Cohort 4: MEDI0382 200 mcg Participants will receive MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). |
Drug: MEDI0382
MEDI0382 administered subcutaneously.
|
| Experimental: Cohort 5: MEDI0382 300 mcg Participants will receive MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). |
Drug: MEDI0382
MEDI0382 administered subcutaneously.
|
| Experimental: Cohort 6: MEDI0382 300 mcg Participants will receive MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). |
Drug: MEDI0382
MEDI0382 administered subcutaneously.
|
Outcome Measures
Primary Outcome Measures
- Percent Change From Baseline in Mixed-meal Test (MMT) Glucose Area Under the Concentration-time Curve From Time 0 to 4 Hours to the End of Treatment (EOT) (Cohort 4) [0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post standardized meal intake (SMI) on Baseline (Day -1) and EOT (Day 41)]
Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hours (hrs) after consumption of the standardized meal (with no additional food intake during this time).
- Change From Baseline in Body Weight to the EOT (Cohort 4) [Baseline (Day 1) and EOT (Day 42)]
Secondary Outcome Measures
- Percent Change From Baseline in MMT Glucose AUC0-4h to the EOT (Cohorts 1, 2, 3, 5, and 6) [0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 22 for Cohort 5; and Day 17 for Cohort 6)]
Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).
- Change From Baseline in Body Weight to the EOT (Cohorts 1, 2, 3, 5, and 6) [Cohort 1: Baseline (Day 1) to EOT (Day 8); Cohort 2: Baseline (Day 1) to EOT (Day 12); Cohort 3: Baseline (Day 1) to EOT (Day 16); Cohort 5: Baseline (Day 1) to EOT (Day 22); Cohort 6: Baseline (Day 1) to EOT (Day 17)]
- Percent Change From Baseline in Hemoglobin A1c (HbA1c) to the EOT (Cohorts 4, 5, and 6) [Cohort 4: Baseline (Day -2) to EOT (Day 42); Cohort 5: Baseline (Day -2) to EOT (Day 22); Cohort 6: Baseline (Day -2) to EOT (Day 17)]
- Change From Baseline in Fructosamine to the EOT (Cohorts 4, 5, and 6) [Cohort 4: Baseline (Day -2) to EOT (Day 41); Cohort 5: Baseline (Day -2) to EOT (Day 22); Cohort 6: Baseline (Day -2) to EOT (Day 17)]
- Change From Baseline in Fasting Glucose Prior to MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6) [Cohort 1: Baseline (Day-1) to EOT (Day7); Cohort 2: Baseline (Day-1) to EOT (Day11); Cohort 3: Baseline (Day-1) to EOT (Day15); Cohort 4: Baseline (Day-1) to EOT (Day41); Cohort 5: Baseline (Day-1) to EOT (Day22); Cohort 6: Baseline (Day-1) to EOT (Day17)]
Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).
- Percent Change From Baseline in Glucose Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24h) After MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6) [0 minutes before; and 15, 30, 45, 60, 90, 120, 180, 240 minutes, and 24 hrs post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4; Day 22 for Cohort 5; and Day 17 for Cohort 6)]
Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])]
An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. Serious adverse events (SAE) is any AE that resulted in death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, life-threatening, a congenital anomaly/birth defect, or an important medical event. TEAEs and TESAEs are defined as AEs and SAEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 28 days after the last study dose of each cohort (approximately 60 days).
- Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs [From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])]
TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 28 days after the last study dose of each cohort (approximately 60 days). Number of participants with TEAEs related to vital signs and physical examination abnormalities were reported.
- Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs [From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])]
TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 28 days after the last study dose of each cohort (approximately 60 days). Number of participants with TEAEs related to ECG abnormalities were reported.
- Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs [From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])]
TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 28 days after the last study dose of each cohort (approximately 60 days). Number of participants with TEAEs related to laboratory abnormalities were reported.
- Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) [Cohort 4: Day -1, and Days 13, 20, 27, 34, and 40; Cohort 5: Day -1 and Day 7-14 post last dose of MEDI0382 (approximately 36 days); Cohort 6: Day -1 and Day 7-14 post last dose of MEDI0382 (approximately 31 days)]
The C-SSRS is an interview-based rating scale to systematically assess suicidal ideation and suicidal behaviour of participants. Yes/No responses are mapped to C-SSRS to assess whether participant experienced suicidal behaviour and suicidal ideation. Suicidal behaviour questions includes preparatory acts or behaviour, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation questions includes wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intent to act, active suicidal ideation with some intent to act (without specific plan), and active suicidal ideation with specific plan and intent. Participants with yes response to any category for suicidal ideation were reported below.
- Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) [Cohort 4: Day -1, and Days 13, 20, 27, 34, and 40; Cohort 5: Day -1 and Day 7-14 post last dose of MEDI0382 (approximately 36 days); Cohort 6: Day -1 and Day 7-14 post last dose of MEDI0382 (approximately 31 days)]
The C-SSRS is an interview-based rating scale to systematically assess suicidal ideation and suicidal behaviour of participants. Yes/No responses are mapped to C-SSRS to assess whether participant experienced suicidal behaviour and suicidal ideation. Suicidal behaviour questions includes preparatory acts or behaviour, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation questions includes wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intent to act, active suicidal ideation with some intent to act (without specific plan), and active suicidal ideation with specific plan and intent. Participants with yes response to any category for suicidal behaviour were reported below.
- Terminal Elimination Half Life (t1/2) of MEDI0382 (Cohorts 1, 2, and 3) [Cohort (C) 1 (Day [D] 1 and [&] D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose; and additional 48 hr post C1D7, C2D11, C3D15 dose]
Terminal elimination half Life is the time measured for the plasma concentration of MEDI0382 to decrease by one half.
- Accumulation Ratio (Rac) of MEDI0382 (Cohorts 1, 2, and 3) [C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose; and additional 48 hr post C1D7, C2D11, C3D15 dose]
Accumulation ratio was calculated as, Rac obtained from area under the curve from time zero to end of dosing interval (AUC[0-tau]) of Nth day divided by AUC(0-tau) of Day 1.
- Area Under the Concentration Time Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) [C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose]
- Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) [C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and additional 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose]
- Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) [C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and additional 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose]
- Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) [C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and additional 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose]
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) [C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and additional 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose]
- Number of Participants With Positive Anti-drug Antibodies to MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) [Day 1 up to 7-14 days post-last dose of MEDI0382 for all cohorts (Approximately 60 days)]
- Percent Change From Baseline in Insulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, 4, 5, and 6) [0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4; Day 22 for Cohort 5; and Day 17 for Cohort 6)]
Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).
- Percent Change From Baseline in Proinsulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) [0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4)]
Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).
- Percent Change From Baseline in C-peptide AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) [0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4)]
Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).
- Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) [0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4)]
Mixes-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time). Incretins included glucagon-like peptide-1 (GLP-1; active and inactive both), glucagon, and gastric inhibitory peptide (GIP).
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Diagnosis of T2DM
-
Must provide written informed consent
-
Body mass index greater than (>) 27 and less than (<) 40 kg/m^2, inclusive
-
Venous access suitable for multiple cannulations
-
Vital signs within normal specified ranges
-
Females must be non-lactating and non-childbearing potential
-
Males must practice 2 effective contraceptive measures if sexually active
Exclusion Criteria:
-
Any concurrent condition that in the opinion of the investigator would interfere with the evaluation of the investigational product
-
History or presence of gastrointestinal, renal, or hepatic disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
-
History of cancer within the last 10 years, with the exception of non-melanoma skin cancer
-
Any clinically important illness (except for T2DM), medical/surgical procedure, or trauma within 4 weeks prior to dosing
-
Fasting glucose greater than or equal to (>=) 200 mg/dL
-
Positive Hepatitis B, Hepatitis C or human immunodeficiency virus test or use of antiretroviral medications at screening.
-
Concurrent or previous use of a glucagon-like peptide 1 receptor agonist
-
Current or previous use of systemic corticosteroids within the past 28 days prior to screening
-
Use of any medicinal products or herbal preparations licensed for control of body weight or appetite is prohibited.
-
Known or suspected history of alcohol or drug abuse within the past 3 years.
-
Positive drug screen
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Berlin | Germany | 10117 | |
| 2 | Research Site | Erfurt | Germany | 99084 | |
| 3 | Research Site | Kiel | Germany | 24105 | |
| 4 | Research Site | Leipzig | Germany | 04103 | |
| 5 | Research Site | Lübeck | Germany | 23538 | |
| 6 | Research Site | Magdeburg | Germany | 39120 | |
| 7 | Research Site | Mainz | Germany | 55116 | |
| 8 | Research Site | Mannheim | Germany | 68167 | |
| 9 | Research Site | München | Germany | 81241 | |
| 10 | Research Site | Neu-Ulm | Germany | 89231 | |
| 11 | Research Site | Neuss | Germany | 41460 |
Sponsors and Collaborators
- MedImmune LLC
Investigators
- Principal Investigator: Michael Stumvoll, Universitätsklinikum Leipzig
Study Documents (Full-Text)
More Information
Additional Information:
- D5670C00002 Protocol_Amendment_8-redacted_correct_PDF-A
- Statistical_Analysis_Plan_MEDI0382_D5670C00002_Redacted_PDF-A
Publications
None provided.Responsible Party:
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT02548585
Other Study ID Numbers:
- D5670C00002
First Posted:
Sep 14, 2015
Last Update Posted:
Apr 5, 2019
Last Verified:
Jan 1, 2019
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by MedImmune LLC
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The study was conducted from 09 Dec 2015 to 24 Feb 2017 in Germany. |
|---|---|
| Pre-assignment Detail | A total of 422 participants were screened, of which 113 participants were randomized in the study. |
| Arm/Group Title | Placebo | Cohort 1: MEDI0382 100 mcg | Cohort 2: MEDI0382 150 mcg | Cohort 3: MEDI0382 200 mcg | Cohort 4: MEDI0382 200 mcg | Cohort 5: MEDI0382 300 mcg | Cohort 6: MEDI0382 300 mcg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received placebo (matched to either 100 micrograms [mcg], or 150 mcg or 200 mcg or 300 mcg of MEDI0382) subcutaneously (SC) once daily from Day 1 to Day 7 (Cohort 1); or Day 1 to Day 11 (Cohort 2); or Day 1 to Day 15 (Cohort 3); or Day 1 to Day 41 (Cohort 4); or Day 1 to Day 22 (Cohort 5); or Day 1 to Day 17 (Cohort 6). | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). |
| Period Title: Overall Study | |||||||
| STARTED | 45 | 6 | 6 | 7 | 25 | 12 | 12 |
| Treated | 45 | 6 | 6 | 7 | 25 | 11 | 12 |
| COMPLETED | 43 | 6 | 6 | 5 | 22 | 10 | 11 |
| NOT COMPLETED | 2 | 0 | 0 | 2 | 3 | 2 | 1 |
Baseline Characteristics
| Arm/Group Title | Placebo | Cohort 1: MEDI0382 100 mcg | Cohort 2: MEDI0382 150 mcg | Cohort 3: MEDI0382 200 mcg | Cohort 4: MEDI0382 200 mcg | Cohort 5: MEDI0382 300 mcg | Cohort 6: MEDI0382 300 mcg | TOTAL |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received placebo (matched to either 100 micrograms [mcg], or 150 mcg or 200 mcg or 300 mcg of MEDI0382) subcutaneously (SC) once daily from Day 1 to Day 7 (Cohort 1); or Day 1 to Day 11 (Cohort 2); or Day 1 to Day 15 (Cohort 3); or Day 1 to Day 41 (Cohort 4); or Day 1 to Day 22 (Cohort 5); or Day 1 to Day 17 (Cohort 6). | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). | Total of all reporting groups |
| Overall Participants | 45 | 6 | 6 | 7 | 25 | 11 | 12 | 112 |
| Age (Years) [Mean (Standard Deviation) ] | ||||||||
| Mean (Standard Deviation) [Years] |
57.2
(6.0)
|
62.5
(2.9)
|
60.2
(4.2)
|
57.0
(4.9)
|
56.0
(7.2)
|
54.8
(6.8)
|
54.6
(6.5)
|
56.9
(6.3)
|
| Sex: Female, Male (Count of Participants) | ||||||||
| Female |
18
40%
|
1
16.7%
|
4
66.7%
|
2
28.6%
|
12
48%
|
4
36.4%
|
3
25%
|
44
39.3%
|
| Male |
27
60%
|
5
83.3%
|
2
33.3%
|
5
71.4%
|
13
52%
|
7
63.6%
|
9
75%
|
68
60.7%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
45
100%
|
6
100%
|
6
100%
|
7
100%
|
25
100%
|
11
100%
|
12
100%
|
112
100%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
2.2%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0.9%
|
| White |
44
97.8%
|
6
100%
|
6
100%
|
7
100%
|
25
100%
|
11
100%
|
12
100%
|
111
99.1%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Percent Change From Baseline in Mixed-meal Test (MMT) Glucose Area Under the Concentration-time Curve From Time 0 to 4 Hours to the End of Treatment (EOT) (Cohort 4) |
|---|---|
| Description | Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hours (hrs) after consumption of the standardized meal (with no additional food intake during this time). |
| Time Frame | 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post standardized meal intake (SMI) on Baseline (Day -1) and EOT (Day 41) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamic (PD) population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample. |
| Arm/Group Title | Cohort 4: Placebo | Cohort 4: MEDI0382 200 mcg |
|---|---|---|
| Arm/Group Description | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). |
| Measure Participants | 26 | 25 |
| Mean (Standard Deviation) [Percent change] |
-9.24
(12.30)
|
-33.81
(18.62)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 4: Placebo, Cohort 4: MEDI0382 200 mcg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | p-value was based on pairwise comparison using analysis of covariance (ANCOVA) adjusted by baseline value. | |
| Title | Change From Baseline in Body Weight to the EOT (Cohort 4) |
|---|---|
| Description | |
| Time Frame | Baseline (Day 1) and EOT (Day 42) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all participants who were randomized and received any study drug and analyzed according to the initial randomization. |
| Arm/Group Title | Cohort 4: Placebo | Cohort 4: MEDI0382 200 mcg |
|---|---|---|
| Arm/Group Description | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). |
| Measure Participants | 26 | 25 |
| Mean (Standard Deviation) [Kilograms (Kg)] |
-1.71
(2.10)
|
-3.83
(2.09)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 4: Placebo, Cohort 4: MEDI0382 200 mcg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0008 |
| Comments | ||
| Method | ANCOVA | |
| Comments | p-value was based on pairwise comparison using ANCOVA adjusted by baseline value. | |
| Title | Percent Change From Baseline in MMT Glucose AUC0-4h to the EOT (Cohorts 1, 2, 3, 5, and 6) |
|---|---|
| Description | Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time). |
| Time Frame | 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 22 for Cohort 5; and Day 17 for Cohort 6) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample. |
| Arm/Group Title | Cohort 1: Placebo | Cohort 1: MEDI0382 100 mcg | Cohort 2: Placebo | Cohort 2: MEDI0382 150 mcg | Cohort 3: Placebo | Cohort 3: MEDI0382 200 mcg | Cohort 5: Placebo | Cohort 5: MEDI0382 300 mcg | Cohort 6: Placebo | Cohort 6: MEDI0382 300 mcg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). | Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). |
| Measure Participants | 3 | 6 | 3 | 6 | 3 | 7 | 5 | 11 | 5 | 12 |
| Mean (Standard Deviation) [Percent change] |
-14.60
(5.56)
|
-41.80
(11.07)
|
-15.07
(13.46)
|
-36.73
(10.09)
|
-0.47
(15.16)
|
-39.58
(5.27)
|
-14.52
(8.12)
|
-41.66
(9.97)
|
-4.80
(3.45)
|
-38.19
(12.51)
|
| Title | Change From Baseline in Body Weight to the EOT (Cohorts 1, 2, 3, 5, and 6) |
|---|---|
| Description | |
| Time Frame | Cohort 1: Baseline (Day 1) to EOT (Day 8); Cohort 2: Baseline (Day 1) to EOT (Day 12); Cohort 3: Baseline (Day 1) to EOT (Day 16); Cohort 5: Baseline (Day 1) to EOT (Day 22); Cohort 6: Baseline (Day 1) to EOT (Day 17) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and received any study drug and analyzed according to the initial randomization. Participants who did not complete the treatment were not included in this analysis. |
| Arm/Group Title | Cohort 1: Placebo | Cohort 1: MEDI0382 100 mcg | Cohort 2: Placebo | Cohort 2: MEDI0382 150 mcg | Cohort 3: Placebo | Cohort 3: MEDI0382 200 mcg | Cohort 5: Placebo | Cohort 5: MEDI0382 300 mcg | Cohort 6: Placebo | Cohort 6: MEDI0382 300 mcg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). | Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). |
| Measure Participants | 3 | 6 | 3 | 6 | 3 | 7 | 5 | 11 | 5 | 12 |
| Mean (Standard Deviation) [Kg] |
-1.20
(0.44)
|
-2.32
(1.29)
|
-1.00
(1.13)
|
-1.52
(0.57)
|
-2.90
(1.05)
|
-4.63
(1.98)
|
-0.98
(2.12)
|
-3.26
(1.99)
|
-0.94
(3.09)
|
-2.04
(1.52)
|
| Title | Percent Change From Baseline in Hemoglobin A1c (HbA1c) to the EOT (Cohorts 4, 5, and 6) |
|---|---|
| Description | |
| Time Frame | Cohort 4: Baseline (Day -2) to EOT (Day 42); Cohort 5: Baseline (Day -2) to EOT (Day 22); Cohort 6: Baseline (Day -2) to EOT (Day 17) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and received any study drug and analyzed according to the initial randomization. Participants who did not complete the treatment were not included in this analysis. |
| Arm/Group Title | Cohort 4: Placebo | Cohort 4: MEDI0382 200 mcg | Cohort 5: Placebo | Cohort 5: MEDI0382 300 mcg | Cohort 6: Placebo | Cohort 6: MEDI0382 300 mcg |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). | Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). |
| Measure Participants | 26 | 25 | 5 | 11 | 5 | 12 |
| Mean (Standard Deviation) [Percent change] |
-0.58
(0.30)
|
-0.92
(0.41)
|
-0.10
(0.29)
|
-0.55
(0.35)
|
-0.18
(0.19)
|
-0.42
(0.27)
|
| Title | Change From Baseline in Fructosamine to the EOT (Cohorts 4, 5, and 6) |
|---|---|
| Description | |
| Time Frame | Cohort 4: Baseline (Day -2) to EOT (Day 41); Cohort 5: Baseline (Day -2) to EOT (Day 22); Cohort 6: Baseline (Day -2) to EOT (Day 17) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and received any study drug and analyzed according to the initial randomization. Participants who did not complete the treatment were not included in this analysis. |
| Arm/Group Title | Cohort 4: Placebo | Cohort 4: MEDI0382 200 mcg | Cohort 5: Placebo | Cohort 5: MEDI0382 300 mcg | Cohort 6: Placebo | Cohort 6: MEDI0382 300 mcg |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). | Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). |
| Measure Participants | 26 | 25 | 5 | 11 | 5 | 12 |
| Mean (Standard Deviation) [micromol/L] |
-33.7
(44.6)
|
-67.9
(44.4)
|
-27.8
(25.8)
|
-47.4
(15.7)
|
-48.8
(43.7)
|
-47.5
(55.3)
|
| Title | Change From Baseline in Fasting Glucose Prior to MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6) |
|---|---|
| Description | Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time). |
| Time Frame | Cohort 1: Baseline (Day-1) to EOT (Day7); Cohort 2: Baseline (Day-1) to EOT (Day11); Cohort 3: Baseline (Day-1) to EOT (Day15); Cohort 4: Baseline (Day-1) to EOT (Day41); Cohort 5: Baseline (Day-1) to EOT (Day22); Cohort 6: Baseline (Day-1) to EOT (Day17) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample. |
| Arm/Group Title | Cohort 1: Placebo | Cohort 1: MEDI0382 100 mcg | Cohort 2: Placebo | Cohort 2: MEDI0382 150 mcg | Cohort 3: Placebo | Cohort 3: MEDI0382 200 mcg | Cohort 4: Placebo | Cohort 4: MEDI0382 200 mcg | Cohort 5: Placebo | Cohort 5: MEDI0382 300 mcg | Cohort 6: Placebo | Cohort 6: MEDI0382 300 mcg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). | Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). |
| Measure Participants | 3 | 6 | 3 | 6 | 3 | 7 | 26 | 25 | 5 | 11 | 5 | 12 |
| Mean (Standard Deviation) [mg/dL] |
-32.44
(17.19)
|
-74.48
(24.59)
|
-49.86
(23.24)
|
-54.06
(19.51)
|
-4.20
(33.73)
|
-63.67
(11.93)
|
-18.52
(18.88)
|
-50.62
(33.61)
|
-32.08
(17.49)
|
-54.42
(19.75)
|
-16.58
(12.45)
|
-55.21
(31.13)
|
| Title | Percent Change From Baseline in Glucose Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24h) After MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6) |
|---|---|
| Description | Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time). |
| Time Frame | 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, 240 minutes, and 24 hrs post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4; Day 22 for Cohort 5; and Day 17 for Cohort 6) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample. |
| Arm/Group Title | Cohort 1: Placebo | Cohort 1: MEDI0382 100 mcg | Cohort 2: Placebo | Cohort 2: MEDI0382 150 mcg | Cohort 3: Placebo | Cohort 3: MEDI0382 200 mcg | Cohort 4: Placebo | Cohort 4: MEDI0382 200 mcg | Cohort 5: Placebo | Cohort 5: MEDI0382 300 mcg | Cohort 6: Placebo | Cohort 6: MEDI0382 300 mcg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). | Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). |
| Measure Participants | 3 | 6 | 3 | 6 | 3 | 7 | 26 | 25 | 5 | 11 | 5 | 12 |
| Mean (Standard Deviation) [Percent change] |
-21.80
(1.41)
|
-28.34
(13.52)
|
0.80
(39.55)
|
-29.32
(17.24)
|
-13.80
(15.95)
|
-27.07
(10.82)
|
-1.06
(11.47)
|
-13.50
(18.19)
|
-4.20
(28.58)
|
-34.51
(11.25)
|
-10.10
(14.69)
|
-26.95
(9.45)
|
| Title | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) |
|---|---|
| Description | An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. Serious adverse events (SAE) is any AE that resulted in death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, life-threatening, a congenital anomaly/birth defect, or an important medical event. TEAEs and TESAEs are defined as AEs and SAEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 28 days after the last study dose of each cohort (approximately 60 days). |
| Time Frame | From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days]) |
Outcome Measure Data
| Analysis Population Description |
|---|
| As-treated Population (ATP) included all participants who received any study drug and analyzed according to the treatment they actually received. |
| Arm/Group Title | Cohort 1: Placebo | Cohort 1: MEDI0382 100 mcg | Cohort 2: Placebo | Cohort 2: MEDI0382 150 mcg | Cohort 3: Placebo | Cohort 3: MEDI0382 200 mcg | Cohort 4: Placebo | Cohort 4: MEDI0382 200 mcg | Cohort 5: Placebo | Cohort 5: MEDI0382 300 mcg | Cohort 6: Placebo | Cohort 6: MEDI0382 300 mcg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). | Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). |
| Measure Participants | 3 | 6 | 3 | 6 | 3 | 7 | 26 | 25 | 5 | 11 | 5 | 12 |
| TEAEs |
2
4.4%
|
6
100%
|
3
50%
|
5
71.4%
|
3
12%
|
7
63.6%
|
23
191.7%
|
22
19.6%
|
4
NaN
|
10
NaN
|
2
NaN
|
10
NaN
|
| TESAEs |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
9.1%
|
1
8.3%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Title | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs |
|---|---|
| Description | TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 28 days after the last study dose of each cohort (approximately 60 days). Number of participants with TEAEs related to vital signs and physical examination abnormalities were reported. |
| Time Frame | From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days]) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ATP included all participants who received any study drug and analyzed according to the treatment they actually received. |
| Arm/Group Title | Cohort 1: Placebo | Cohort 1: MEDI0382 100 mcg | Cohort 2: Placebo | Cohort 2: MEDI0382 150 mcg | Cohort 3: Placebo | Cohort 3: MEDI0382 200 mcg | Cohort 4: Placebo | Cohort 4: MEDI0382 200 mcg | Cohort 5: Placebo | Cohort 5: MEDI0382 300 mcg | Cohort 6: Placebo | Cohort 6: MEDI0382 300 mcg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). | Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). |
| Measure Participants | 3 | 6 | 3 | 6 | 3 | 7 | 26 | 25 | 5 | 11 | 5 | 12 |
| Blood Pressure increased |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
16.7%
|
1
0.9%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Blood pressure systolic increased |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
1
NaN
|
1
NaN
|
0
NaN
|
| Blood pressure diastolic increased |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
1
NaN
|
| Physical Examinations |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Title | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs |
|---|---|
| Description | TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 28 days after the last study dose of each cohort (approximately 60 days). Number of participants with TEAEs related to ECG abnormalities were reported. |
| Time Frame | From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days]) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ATP included all participants who received any study drug and analyzed according to the treatment they actually received. |
| Arm/Group Title | Cohort 1: Placebo | Cohort 1: MEDI0382 100 mcg | Cohort 2: Placebo | Cohort 2: MEDI0382 150 mcg | Cohort 3: Placebo | Cohort 3: MEDI0382 200 mcg | Cohort 4: Placebo | Cohort 4: MEDI0382 200 mcg | Cohort 5: Placebo | Cohort 5: MEDI0382 300 mcg | Cohort 6: Placebo | Cohort 6: MEDI0382 300 mcg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). | Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). |
| Measure Participants | 3 | 6 | 3 | 6 | 3 | 7 | 26 | 25 | 5 | 11 | 5 | 12 |
| Arrhythmia |
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Atrial fibrillation |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0.9%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Atrioventricular block first degree |
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Atrioventricular block second degree |
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Electrocardiogram ST segment depression |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
9.1%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Extrasystoles |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
1
4%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Sinus tachycardia |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0.9%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Supraventricular extrasystoles |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
8.3%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Supraventricular tachycardia |
1
2.2%
|
1
16.7%
|
1
16.7%
|
0
0%
|
1
4%
|
1
9.1%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Tachycardia |
0
0%
|
1
16.7%
|
0
0%
|
1
14.3%
|
0
0%
|
1
9.1%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Ventricular extrasystoles |
0
0%
|
1
16.7%
|
1
16.7%
|
1
14.3%
|
0
0%
|
0
0%
|
1
8.3%
|
1
0.9%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Ventricular tachycardia |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
4%
|
1
9.1%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Title | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs |
|---|---|
| Description | TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 28 days after the last study dose of each cohort (approximately 60 days). Number of participants with TEAEs related to laboratory abnormalities were reported. |
| Time Frame | From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days]) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ATP included all participants who received any study drug and analyzed according to the treatment they actually received. |
| Arm/Group Title | Cohort 1: Placebo | Cohort 1: MEDI0382 100 mcg | Cohort 2: Placebo | Cohort 2: MEDI0382 150 mcg | Cohort 3: Placebo | Cohort 3: MEDI0382 200 mcg | Cohort 4: Placebo | Cohort 4: MEDI0382 200 mcg | Cohort 5: Placebo | Cohort 5: MEDI0382 300 mcg | Cohort 6: Placebo | Cohort 6: MEDI0382 300 mcg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). | Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). |
| Measure Participants | 3 | 6 | 3 | 6 | 3 | 7 | 26 | 25 | 5 | 11 | 5 | 12 |
| Lipase increased |
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
1
0.9%
|
0
NaN
|
2
NaN
|
0
NaN
|
1
NaN
|
| Hypokalemia |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
8.3%
|
1
0.9%
|
0
NaN
|
0
NaN
|
0
NaN
|
1
NaN
|
| C-reactive protein increased |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
9.1%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Hypoglycemia |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0.9%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Chromaturia |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0.9%
|
0
NaN
|
1
NaN
|
0
NaN
|
0
NaN
|
| Title | Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) |
|---|---|
| Description | The C-SSRS is an interview-based rating scale to systematically assess suicidal ideation and suicidal behaviour of participants. Yes/No responses are mapped to C-SSRS to assess whether participant experienced suicidal behaviour and suicidal ideation. Suicidal behaviour questions includes preparatory acts or behaviour, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation questions includes wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intent to act, active suicidal ideation with some intent to act (without specific plan), and active suicidal ideation with specific plan and intent. Participants with yes response to any category for suicidal ideation were reported below. |
| Time Frame | Cohort 4: Day -1, and Days 13, 20, 27, 34, and 40; Cohort 5: Day -1 and Day 7-14 post last dose of MEDI0382 (approximately 36 days); Cohort 6: Day -1 and Day 7-14 post last dose of MEDI0382 (approximately 31 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ATP included all participants who received any study drug and analyzed according to the treatment they actually received. |
| Arm/Group Title | Cohort 4: Placebo | Cohort 4: MEDI0382 200 mcg | Cohort 5: Placebo | Cohort 5: MEDI0382 300 mcg | Cohort 6: Placebo | Cohort 6: MEDI0382 300 mcg |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). | Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). |
| Measure Participants | 26 | 25 | 5 | 11 | 5 | 12 |
| Day -1 |
1
2.2%
|
4
66.7%
|
0
0%
|
2
28.6%
|
0
0%
|
2
18.2%
|
| Day 13 |
1
2.2%
|
0
0%
|
||||
| Day 20 |
0
0%
|
0
0%
|
||||
| Day 27 |
0
0%
|
0
0%
|
||||
| Day 34 |
0
0%
|
0
0%
|
||||
| Day 40 |
0
0%
|
0
0%
|
||||
| Days 7-14 post last dose of MEDI0382 |
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) |
|---|---|
| Description | The C-SSRS is an interview-based rating scale to systematically assess suicidal ideation and suicidal behaviour of participants. Yes/No responses are mapped to C-SSRS to assess whether participant experienced suicidal behaviour and suicidal ideation. Suicidal behaviour questions includes preparatory acts or behaviour, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation questions includes wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intent to act, active suicidal ideation with some intent to act (without specific plan), and active suicidal ideation with specific plan and intent. Participants with yes response to any category for suicidal behaviour were reported below. |
| Time Frame | Cohort 4: Day -1, and Days 13, 20, 27, 34, and 40; Cohort 5: Day -1 and Day 7-14 post last dose of MEDI0382 (approximately 36 days); Cohort 6: Day -1 and Day 7-14 post last dose of MEDI0382 (approximately 31 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ATP included all participants who received any study drug and analyzed according to the treatment they actually received. |
| Arm/Group Title | Cohort 4: Placebo | Cohort 4: MEDI0382 200 mcg | Cohort 5: Placebo | Cohort 5: MEDI0382 300 mcg | Cohort 6: Placebo | Cohort 6: MEDI0382 300 mcg |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). | Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). |
| Measure Participants | 26 | 25 | 5 | 11 | 5 | 12 |
| Day -1 |
2
4.4%
|
2
33.3%
|
0
0%
|
1
14.3%
|
0
0%
|
1
9.1%
|
| Day 13 |
1
2.2%
|
0
0%
|
||||
| Day 20 |
0
0%
|
0
0%
|
||||
| Day 27 |
0
0%
|
0
0%
|
||||
| Day 34 |
0
0%
|
0
0%
|
||||
| Day 40 |
0
0%
|
0
0%
|
||||
| Days 7-14 post last dose of MEDI0382 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Terminal Elimination Half Life (t1/2) of MEDI0382 (Cohorts 1, 2, and 3) |
|---|---|
| Description | Terminal elimination half Life is the time measured for the plasma concentration of MEDI0382 to decrease by one half. |
| Time Frame | Cohort (C) 1 (Day [D] 1 and [&] D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose; and additional 48 hr post C1D7, C2D11, C3D15 dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) population included all participants who received at least 1 dose of study drug and had at least one PK sample taken that was above the lower limit of quantitation. |
| Arm/Group Title | Cohort 1: MEDI0382 100 mcg | Cohort 2: MEDI0382 150 mcg | Cohort 3: MEDI0382 200 mcg |
|---|---|---|---|
| Arm/Group Description | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). |
| Measure Participants | 6 | 6 | 7 |
| Day 1 |
8.5
|
||
| Day 5 |
10.3
|
||
| Day 7 |
11.7
|
||
| Day 9 |
8.3
|
||
| Day 11 |
11.3
|
||
| Day 15 |
11.3
|
| Title | Accumulation Ratio (Rac) of MEDI0382 (Cohorts 1, 2, and 3) |
|---|---|
| Description | Accumulation ratio was calculated as, Rac obtained from area under the curve from time zero to end of dosing interval (AUC[0-tau]) of Nth day divided by AUC(0-tau) of Day 1. |
| Time Frame | C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose; and additional 48 hr post C1D7, C2D11, C3D15 dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population included all participants who received at least 1 dose of study drug and had at least one PK sample taken that was above the lower limit of quantitation. |
| Arm/Group Title | Cohort 1: MEDI0382 100 mcg | Cohort 2: MEDI0382 150 mcg | Cohort 3: MEDI0382 200 mcg |
|---|---|---|---|
| Arm/Group Description | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). |
| Measure Participants | 6 | 6 | 7 |
| Day 1 |
NA
|
||
| Day 5 |
NA
|
||
| Day 7 |
1.3
|
||
| Day 9 |
NA
|
||
| Day 11 |
1.1
|
||
| Day 15 |
1.3
|
| Title | Area Under the Concentration Time Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) |
|---|---|
| Description | |
| Time Frame | C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population included all participants who received at least 1 dose of study drug and had at least one PK sample taken that was above the lower limit of quantitation. |
| Arm/Group Title | Cohort 1: MEDI0382 100 mcg | Cohort 2: MEDI0382 150 mcg | Cohort 3: MEDI0382 200 mcg | Cohort 4: MEDI0382 200 mcg | Cohort 5: MEDI0382 300 mcg | Cohort 6: MEDI0382 300 mcg |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). |
| Measure Participants | 6 | 6 | 7 | 25 | 11 | 12 |
| Day 1 |
82.21
|
|||||
| Day 5 |
174.58
|
|||||
| Day 7 |
107.01
|
|||||
| Day 9 |
194.78
|
164.05
|
||||
| Day 11 |
157.31
|
275.29
|
||||
| Day 15 |
195.40
|
|||||
| Day 16 |
261.90
|
|||||
| Day 17 |
246.06
|
|||||
| Day 22 |
254.35
|
|||||
| Day 41 |
199.10
|
| Title | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) |
|---|---|
| Description | |
| Time Frame | C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and additional 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population included all participants who received at least 1 dose of study drug and had at least one PK sample taken that was above the lower limit of quantitation. |
| Arm/Group Title | Cohort 1: MEDI0382 100 mcg | Cohort 2: MEDI0382 150 mcg | Cohort 3: MEDI0382 200 mcg | Cohort 4: MEDI0382 200 mcg | Cohort 5: MEDI0382 300 mcg | Cohort 6: MEDI0382 300 mcg |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). |
| Measure Participants | 6 | 6 | 7 | 25 | 11 | 12 |
| Day 1 |
103.46
|
|||||
| Day 5 |
207.15
|
|||||
| Day 7 |
184.68
|
|||||
| Day 9 |
242.60
|
238.22
|
||||
| Day 11 |
215.80
|
|||||
| Day 15 |
271.84
|
|||||
| Day 16 |
317.93
|
|||||
| Day 17 |
327.28
|
|||||
| Day 22 |
294.60
|
|||||
| Day 41 |
262.17
|
| Title | Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) |
|---|---|
| Description | |
| Time Frame | C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and additional 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population included all participants who received at least 1 dose of study drug and had at least one PK sample taken that was above the lower limit of quantitation. |
| Arm/Group Title | Cohort 1: MEDI0382 100 mcg | Cohort 2: MEDI0382 150 mcg | Cohort 3: MEDI0382 200 mcg | Cohort 4: MEDI0382 200 mcg | Cohort 5: MEDI0382 300 mcg | Cohort 6: MEDI0382 300 mcg |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). |
| Measure Participants | 6 | 6 | 7 | 25 | 11 | 12 |
| Day 1 |
4.97
|
|||||
| Day 5 |
9.66
|
|||||
| Day 7 |
6.26
|
|||||
| Day 9 |
10.57
|
11.64
|
||||
| Day 11 |
9.57
|
13.69
|
||||
| Day 15 |
10.97
|
|||||
| Day 16 |
17.65
|
|||||
| Day 17 |
15.55
|
|||||
| Day 22 |
15.77
|
|||||
| Day 41 |
13.42
|
| Title | Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) |
|---|---|
| Description | |
| Time Frame | C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and additional 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population included all participants who received at least 1 dose of study drug and had at least one PK sample taken that was above the lower limit of quantitation. |
| Arm/Group Title | Cohort 1: MEDI0382 100 mcg | Cohort 2: MEDI0382 150 mcg | Cohort 3: MEDI0382 200 mcg | Cohort 4: MEDI0382 200 mcg | Cohort 5: MEDI0382 300 mcg | Cohort 6: MEDI0382 300 mcg |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). |
| Measure Participants | 6 | 6 | 7 | 25 | 11 | 12 |
| Day 1 |
0.705
|
|||||
| Day 5 |
2.685
|
|||||
| Day 7 |
2.372
|
|||||
| Day 9 |
3.521
|
2.635
|
||||
| Day 11 |
3.59
|
3.586
|
||||
| Day 15 |
4.973
|
|||||
| Day 16 |
4.062
|
|||||
| Day 17 |
4.766
|
|||||
| Day 22 |
5.21
|
|||||
| Day 41 |
3.38
|
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) |
|---|---|
| Description | |
| Time Frame | C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and additional 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population included all participants who received at least 1 dose of study drug and had at least one PK sample taken that was above the lower limit of quantitation. |
| Arm/Group Title | Cohort 1: MEDI0382 100 mcg | Cohort 2: MEDI0382 150 mcg | Cohort 3: MEDI0382 200 mcg | Cohort 4: MEDI0382 200 mcg | Cohort 5: MEDI0382 300 mcg | Cohort 6: MEDI0382 300 mcg |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). |
| Measure Participants | 6 | 6 | 7 | 25 | 11 | 12 |
| Day 1 |
8
|
|||||
| Day 5 |
6
|
|||||
| Day 7 |
6
|
|||||
| Day 9 |
6
|
4
|
||||
| Day 11 |
6
|
6
|
||||
| Day 15 |
6
|
|||||
| Day 16 |
4
|
|||||
| Day 17 |
4
|
|||||
| Day 22 |
4
|
|||||
| Day 41 |
4
|
| Title | Number of Participants With Positive Anti-drug Antibodies to MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) |
|---|---|
| Description | |
| Time Frame | Day 1 up to 7-14 days post-last dose of MEDI0382 for all cohorts (Approximately 60 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ATP included all participants who received any study drug and analyzed according to the treatment they actually received. |
| Arm/Group Title | Cohort 1: Placebo | Cohort 1: MEDI0382 100 mcg | Cohort 2: Placebo | Cohort 2: MEDI0382 150 mcg | Cohort 3: Placebo | Cohort 3: MEDI0382 200 mcg | Cohort 4: Placebo | Cohort 4: MEDI0382 200 mcg | Cohort 5: Placebo | Cohort 5: MEDI0382 300 mcg | Cohort 6: Placebo | Cohort 6: MEDI0382 300 mcg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). | Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). |
| Measure Participants | 3 | 6 | 3 | 6 | 3 | 7 | 26 | 25 | 5 | 11 | 5 | 12 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Title | Percent Change From Baseline in Insulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, 4, 5, and 6) |
|---|---|
| Description | Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time). |
| Time Frame | 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4; Day 22 for Cohort 5; and Day 17 for Cohort 6) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample. |
| Arm/Group Title | Cohort 1: Placebo | Cohort 1: MEDI0382 100 mcg | Cohort 2: Placebo | Cohort 2: MEDI0382 150 mcg | Cohort 3: Placebo | Cohort 3: MEDI0382 200 mcg | Cohort 4: Placebo | Cohort 4: MEDI0382 200 mcg | Cohort 5: Placebo | Cohort 5: MEDI0382 300 mcg | Cohort 6: Placebo | Cohort 6: MEDI0382 300 mcg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). | Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). |
| Measure Participants | 3 | 6 | 3 | 6 | 3 | 7 | 26 | 25 | 5 | 11 | 5 | 12 |
| Mean (Standard Deviation) [Percent change] |
10.83
(21.33)
|
-9.37
(29.17)
|
-3.67
(13.76)
|
36.32
(35.21)
|
-20.43
(68.82)
|
-17.47
(38.84)
|
-8.63
(32.33)
|
-1.17
(44.20)
|
-17.70
(16.47)
|
1.01
(31.00)
|
-8.18
(28.34)
|
-7.72
(37.03)
|
| Title | Percent Change From Baseline in Proinsulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) |
|---|---|
| Description | Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time). |
| Time Frame | 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample. |
| Arm/Group Title | Cohort 1: Placebo | Cohort 1: MEDI0382 100 mcg | Cohort 2: Placebo | Cohort 2: MEDI0382 150 mcg | Cohort 3: Placebo | Cohort 3: MEDI0382 200 mcg | Cohort 4: Placebo | Cohort 4: MEDI0382 200 mcg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). |
| Measure Participants | 3 | 6 | 3 | 6 | 3 | 7 | 26 | 25 |
| Mean (Standard Deviation) [Percent change] |
-3.27
(38.92)
|
-52.10
(36.29)
|
-33.13
(40.07)
|
-36.77
(19.62)
|
81.27
(77.21)
|
-54.13
(26.40)
|
-29.72
(31.13)
|
-47.93
(22.12)
|
| Title | Percent Change From Baseline in C-peptide AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) |
|---|---|
| Description | Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time). |
| Time Frame | 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample. |
| Arm/Group Title | Cohort 1: Placebo | Cohort 1: MEDI0382 100 mcg | Cohort 2: Placebo | Cohort 2: MEDI0382 150 mcg | Cohort 3: Placebo | Cohort 3: MEDI0382 200 mcg | Cohort 4: Placebo | Cohort 4: MEDI0382 200 mcg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). |
| Measure Participants | 3 | 6 | 3 | 6 | 3 | 7 | 26 | 25 |
| Mean (Standard Deviation) [Percent change] |
10.17
(5.05)
|
-3.82
(21.29)
|
-1.43
(6.02)
|
39.78
(32.88)
|
79.37
(91.56)
|
-9.07
(27.27)
|
8.08
(32.12)
|
15.66
(42.35)
|
| Title | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) |
|---|---|
| Description | Mixes-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time). Incretins included glucagon-like peptide-1 (GLP-1; active and inactive both), glucagon, and gastric inhibitory peptide (GIP). |
| Time Frame | 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample. |
| Arm/Group Title | Cohort 1: Placebo | Cohort 1: MEDI0382 100 mcg | Cohort 2: Placebo | Cohort 2: MEDI0382 150 mcg | Cohort 3: Placebo | Cohort 3: MEDI0382 200 mcg | Cohort 4: Placebo | Cohort 4: MEDI0382 200 mcg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). |
| Measure Participants | 3 | 6 | 3 | 6 | 3 | 7 | 26 | 25 |
| GLP-1, Active: Change at EOT |
8.30
(13.15)
|
-33.67
(16.84)
|
-10.40
(10.47)
|
-50.45
(12.30)
|
-2.87
(20.32)
|
-40.36
(26.90)
|
1.63
(26.43)
|
-49.73
(22.88)
|
| GLP-1, Inactive: Change at EOT |
-20.30
(NA)
|
0.70
(NA)
|
-22.90
(NA)
|
-10.93
(22.36)
|
1.75
(29.20)
|
-8.07
(11.30)
|
3.99
(29.59)
|
-28.85
(16.73)
|
| Glucagon: Change at EOT |
-13.85
(18.60)
|
-20.25
(25.45)
|
-17.53
(19.46)
|
-38.12
(16.33)
|
-18.73
(21.59)
|
-3.05
(36.56)
|
-1.76
(21.47)
|
-30.17
(25.56)
|
| GIP: Change at EOT |
18.00
(2.83)
|
-46.50
(14.85)
|
4.10
(24.61)
|
-27.08
(25.03)
|
-6.30
(7.35)
|
-21.34
(39.48)
|
-6.60
(19.43)
|
-37.38
(23.14)
|
Adverse Events
| Time Frame | From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days]) | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||||||||||
| Arm/Group Title | Cohort 1: Placebo | Cohort 1: MEDI0382 100 mcg | Cohort 2: Placebo | Cohort 2: MEDI0382 150 mcg | Cohort 3: Placebo | Cohort 3: MEDI0382 200 mcg | Cohort 4: Placebo | Cohort 4: MEDI0382 200 mcg | Cohort 5: Placebo | Cohort 5: MEDI0382 300 mcg | Cohort 6: Placebo | Cohort 6: MEDI0382 300 mcg | ||||||||||||
| Arm/Group Description | Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7. | Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). ) | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41). | Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). | Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). | Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17). | Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). | ||||||||||||
All Cause Mortality |
||||||||||||||||||||||||
| Cohort 1: Placebo | Cohort 1: MEDI0382 100 mcg | Cohort 2: Placebo | Cohort 2: MEDI0382 150 mcg | Cohort 3: Placebo | Cohort 3: MEDI0382 200 mcg | Cohort 4: Placebo | Cohort 4: MEDI0382 200 mcg | Cohort 5: Placebo | Cohort 5: MEDI0382 300 mcg | Cohort 6: Placebo | Cohort 6: MEDI0382 300 mcg | |||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/3 (0%) | 0/7 (0%) | 0/26 (0%) | 0/25 (0%) | 0/5 (0%) | 0/11 (0%) | 0/5 (0%) | 0/12 (0%) | ||||||||||||
Serious Adverse Events |
||||||||||||||||||||||||
| Cohort 1: Placebo | Cohort 1: MEDI0382 100 mcg | Cohort 2: Placebo | Cohort 2: MEDI0382 150 mcg | Cohort 3: Placebo | Cohort 3: MEDI0382 200 mcg | Cohort 4: Placebo | Cohort 4: MEDI0382 200 mcg | Cohort 5: Placebo | Cohort 5: MEDI0382 300 mcg | Cohort 6: Placebo | Cohort 6: MEDI0382 300 mcg | |||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 0/6 (0%) | 0/3 (0%) | 0/6 (0%) | 0/3 (0%) | 1/7 (14.3%) | 1/26 (3.8%) | 0/25 (0%) | 0/5 (0%) | 0/11 (0%) | 0/5 (0%) | 0/12 (0%) | ||||||||||||
| Eye disorders | ||||||||||||||||||||||||
| Diplopia | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Infections and infestations | ||||||||||||||||||||||||
| Pneumonia mycoplasmal | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||||
| Cohort 1: Placebo | Cohort 1: MEDI0382 100 mcg | Cohort 2: Placebo | Cohort 2: MEDI0382 150 mcg | Cohort 3: Placebo | Cohort 3: MEDI0382 200 mcg | Cohort 4: Placebo | Cohort 4: MEDI0382 200 mcg | Cohort 5: Placebo | Cohort 5: MEDI0382 300 mcg | Cohort 6: Placebo | Cohort 6: MEDI0382 300 mcg | |||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/3 (66.7%) | 6/6 (100%) | 3/3 (100%) | 5/6 (83.3%) | 3/3 (100%) | 7/7 (100%) | 23/26 (88.5%) | 22/25 (88%) | 4/5 (80%) | 10/11 (90.9%) | 2/5 (40%) | 10/12 (83.3%) | ||||||||||||
| Cardiac disorders | ||||||||||||||||||||||||
| Angina pectoris | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Atrial fibrillation | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Atrioventricular block first degree | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Atrioventricular block second degree | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Extrasystoles | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 2 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Palpitations | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Sinus tachycardia | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Supraventricular extrasystoles | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Supraventricular tachycardia | 1/3 (33.3%) | 7 | 1/6 (16.7%) | 1 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 1/3 (33.3%) | 1 | 1/7 (14.3%) | 1 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Tachycardia | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Ventricular extrasystoles | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 3 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Ventricular tachycardia | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 1/7 (14.3%) | 1 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Arrhythmia | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||||||||||||||||||
| Vertigo positional | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Eye disorders | ||||||||||||||||||||||||
| Abnormal sensation in eye | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Vision blurred | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 2/7 (28.6%) | 2 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 1/12 (8.3%) | 1 |
| Visual acuity reduced | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||||||||||
| Abdominal discomfort | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 3/25 (12%) | 3 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Abdominal distension | 0/3 (0%) | 0 | 3/6 (50%) | 3 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/26 (0%) | 0 | 6/25 (24%) | 9 | 0/5 (0%) | 0 | 2/11 (18.2%) | 2 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Abdominal pain | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 2/7 (28.6%) | 2 | 1/26 (3.8%) | 1 | 1/25 (4%) | 4 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Abdominal pain lower | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Abdominal pain upper | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 1/12 (8.3%) | 1 |
| Constipation | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 3/26 (11.5%) | 5 | 6/25 (24%) | 7 | 1/5 (20%) | 1 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 1/12 (8.3%) | 1 |
| Diarrhoea | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/3 (33.3%) | 8 | 1/7 (14.3%) | 2 | 3/26 (11.5%) | 4 | 4/25 (16%) | 6 | 1/5 (20%) | 1 | 1/11 (9.1%) | 2 | 0/5 (0%) | 0 | 2/12 (16.7%) | 2 |
| Dry mouth | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 1/12 (8.3%) | 1 |
| Dyspepsia | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 3/7 (42.9%) | 3 | 1/26 (3.8%) | 1 | 7/25 (28%) | 7 | 0/5 (0%) | 0 | 4/11 (36.4%) | 7 | 0/5 (0%) | 0 | 2/12 (16.7%) | 2 |
| Eructation | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 4/25 (16%) | 4 | 0/5 (0%) | 0 | 3/11 (27.3%) | 3 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Faeces discoloured | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 2/11 (18.2%) | 2 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Faeces hard | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 1/12 (8.3%) | 1 |
| Faeces soft | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 2/26 (7.7%) | 3 | 2/25 (8%) | 2 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Flatulence | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Gastrooesophageal reflux disease | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 1/11 (9.1%) | 1 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Infrequent bowel movements | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 1/11 (9.1%) | 1 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Intra-abdominal haematoma | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 1/5 (20%) | 1 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Nausea | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 3/6 (50%) | 7 | 0/3 (0%) | 0 | 3/7 (42.9%) | 4 | 5/26 (19.2%) | 7 | 13/25 (52%) | 39 | 1/5 (20%) | 2 | 3/11 (27.3%) | 6 | 0/5 (0%) | 0 | 5/12 (41.7%) | 7 |
| Pancreatolithiasis | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Regurgitation | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 1/11 (9.1%) | 1 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Salivary hypersecretion | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 1/11 (9.1%) | 1 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Vomiting | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 0/3 (0%) | 0 | 3/7 (42.9%) | 8 | 0/26 (0%) | 0 | 8/25 (32%) | 40 | 0/5 (0%) | 0 | 3/11 (27.3%) | 9 | 0/5 (0%) | 0 | 1/12 (8.3%) | 2 |
| General disorders | ||||||||||||||||||||||||
| Asthenia | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 1/12 (8.3%) | 2 |
| Early satiety | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 2/11 (18.2%) | 2 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Fatigue | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/26 (0%) | 0 | 5/25 (20%) | 5 | 0/5 (0%) | 0 | 2/11 (18.2%) | 2 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Feeling hot | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Injection site discolouration | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Injection site erythema | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 3/25 (12%) | 4 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Injection site haematoma | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Injection site haemorrhage | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 5 | 0/7 (0%) | 0 | 2/26 (7.7%) | 2 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Injection site pain | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 2/25 (8%) | 3 | 0/5 (0%) | 0 | 2/11 (18.2%) | 2 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Injection site pruritus | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Injection site reaction | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 6 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Malaise | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 2 | 0/5 (0%) | 0 | 1/11 (9.1%) | 1 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Medical device site erosion | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Medical device site erythema | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 2/26 (7.7%) | 2 | 3/25 (12%) | 3 | 0/5 (0%) | 0 | 1/11 (9.1%) | 1 | 0/5 (0%) | 0 | 1/12 (8.3%) | 1 |
| Medical device site injury | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Medical device site irritation | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 3/26 (11.5%) | 3 | 3/25 (12%) | 4 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Medical device site pain | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Medical device site pruritus | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 2/26 (7.7%) | 2 | 3/25 (12%) | 3 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Medical device site rash | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Medical device site reaction | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Oedema peripheral | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Immune system disorders | ||||||||||||||||||||||||
| Allergic oedema | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Infections and infestations | ||||||||||||||||||||||||
| Bronchitis | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Cellulitis | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Escherichia urinary tract infection | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 1/5 (20%) | 1 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Gastrointestinal infection | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Influenza | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Nasopharyngitis | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 6/26 (23.1%) | 7 | 4/25 (16%) | 4 | 1/5 (20%) | 1 | 2/11 (18.2%) | 2 | 1/5 (20%) | 1 | 3/12 (25%) | 3 |
| Tonsillitis | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 1/12 (8.3%) | 1 |
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||
| Burns second degree | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 1/5 (20%) | 1 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Ligament sprain | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 1/12 (8.3%) | 1 |
| Skin abrasion | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Investigations | ||||||||||||||||||||||||
| Alanine aminotransferase increased | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Blood pressure diastolic increased | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 1/12 (8.3%) | 1 |
| Blood pressure increased | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 2/26 (7.7%) | 6 | 1/25 (4%) | 5 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Blood pressure systolic increased | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 1/11 (9.1%) | 1 | 1/5 (20%) | 4 | 0/12 (0%) | 0 |
| Body temperature increased | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| C-reactive protein increased | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Electrocardiogram st segment depression | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Heart rate increased | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Lipase increased | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 2/11 (18.2%) | 3 | 0/5 (0%) | 0 | 1/12 (8.3%) | 1 |
| Metabolism and nutrition disorders | ||||||||||||||||||||||||
| Decreased appetite | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 1/3 (33.3%) | 1 | 6/7 (85.7%) | 6 | 0/26 (0%) | 0 | 5/25 (20%) | 5 | 1/5 (20%) | 1 | 4/11 (36.4%) | 4 | 0/5 (0%) | 0 | 3/12 (25%) | 3 |
| Hypoglycaemia | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Hypokalaemia | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 2 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 1/12 (8.3%) | 1 |
| Increased appetite | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||
| Ankle deformity | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 1/11 (9.1%) | 1 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Arthralgia | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Back pain | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 2/7 (28.6%) | 2 | 1/26 (3.8%) | 1 | 2/25 (8%) | 2 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Flank pain | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 2 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Musculoskeletal chest pain | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Myalgia | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Neck pain | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Pain in extremity | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 2/7 (28.6%) | 2 | 1/26 (3.8%) | 1 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||||||||||
| Dizziness | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 5/26 (19.2%) | 6 | 4/25 (16%) | 6 | 0/5 (0%) | 0 | 1/11 (9.1%) | 2 | 0/5 (0%) | 0 | 2/12 (16.7%) | 2 |
| Dizziness postural | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 1/11 (9.1%) | 1 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Dysgeusia | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 2/25 (8%) | 2 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 1/12 (8.3%) | 1 |
| Headache | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 3 | 1/3 (33.3%) | 6 | 4/7 (57.1%) | 6 | 2/26 (7.7%) | 6 | 9/25 (36%) | 10 | 1/5 (20%) | 1 | 3/11 (27.3%) | 3 | 1/5 (20%) | 1 | 1/12 (8.3%) | 1 |
| Paraesthesia | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 1/12 (8.3%) | 1 |
| Presyncope | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Sciatica | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Somnolence | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||||||||||
| Restlessness | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||||||||||
| Chromaturia | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 1/11 (9.1%) | 1 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Micturition urgency | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 2/12 (16.7%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||
| Cough | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 1/5 (20%) | 1 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 1/12 (8.3%) | 1 |
| Dysphonia | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 4 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Dyspnoea exertional | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/7 (14.3%) | 1 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Nasal congestion | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Nasal mucosal ulcer | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||
| Alopecia | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 2/25 (8%) | 2 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Dermatitis contact | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 1/5 (20%) | 1 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Erythema | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 1/25 (4%) | 1 | 1/5 (20%) | 1 | 1/11 (9.1%) | 1 | 0/5 (0%) | 0 | 3/12 (25%) | 4 |
| Pruritus | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 1/25 (4%) | 1 | 0/5 (0%) | 0 | 1/11 (9.1%) | 1 | 0/5 (0%) | 0 | 2/12 (16.7%) | 2 |
| Rash | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 3/25 (12%) | 3 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Skin reaction | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Vascular disorders | ||||||||||||||||||||||||
| Haemorrhage | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Hypotension | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Phlebitis | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 1/26 (3.8%) | 1 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
| Thrombophlebitis | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/7 (0%) | 0 | 0/26 (0%) | 0 | 0/25 (0%) | 0 | 0/5 (0%) | 0 | 0/11 (0%) | 0 | 0/5 (0%) | 0 | 0/12 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
MedImmune has 60 days to review results communications prior to public release and may delete information that compromises on-going studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
Results Point of Contact
| Name/Title | Philip Ambery |
|---|---|
| Organization | MedImmune, LLC |
| Phone | +44 (0) 1223 895997 |
| information.center@astrazeneca.com |
Responsible Party:
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT02548585
Other Study ID Numbers:
- D5670C00002
First Posted:
Sep 14, 2015
Last Update Posted:
Apr 5, 2019
Last Verified:
Jan 1, 2019