Type 2 Diabetes Mellitus
Conditions
Keywords
MEDI0382, diabetes
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).
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).
Interventions
DRUGMEDI0382
MEDI0382 administered subcutaneously.
DRUGPlacebo
Placebo administered subcutaneously.
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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). |
| 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). |
| 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. |
| 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) | — |
Countries
Germany
Participant flow
Recruitment details
The study was conducted from 09 Dec 2015 to 24 Feb 2017 in Germany.
Pre-assignment details
A total of 422 participants were screened, of which 113 participants were randomized in the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo 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). | 45 |
| Cohort 1: MEDI0382 100 mcg Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. | 6 |
| Cohort 2: MEDI0382 150 mcg 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). | 6 |
| Cohort 3: MEDI0382 200 mcg 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). | 7 |
| Cohort 4: MEDI0382 200 mcg 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). | 25 |
| Cohort 5: MEDI0382 300 mcg 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). | 11 |
| Cohort 6: MEDI0382 300 mcg 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). | 12 |
| TOTAL Total of all reporting groups | 112 |
| Total | 224 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Other | 1 | 0 | 0 | 2 | 3 | 0 | 1 |
| Overall Study | Randomized but not treated | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | 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 |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 57.2 Years STANDARD_DEVIATION 6 | 62.5 Years STANDARD_DEVIATION 2.9 | 60.2 Years STANDARD_DEVIATION 4.2 | 57.0 Years STANDARD_DEVIATION 4.9 | 56.0 Years STANDARD_DEVIATION 7.2 | 54.8 Years STANDARD_DEVIATION 6.8 | 54.6 Years STANDARD_DEVIATION 6.5 | 56.9 Years STANDARD_DEVIATION 6.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 45 Participants | 6 Participants | 6 Participants | 7 Participants | 25 Participants | 11 Participants | 12 Participants | 112 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 44 Participants | 6 Participants | 6 Participants | 7 Participants | 25 Participants | 11 Participants | 12 Participants | 111 Participants |
| Sex: Female, Male Female | 18 Participants | 1 Participants | 4 Participants | 2 Participants | 12 Participants | 4 Participants | 3 Participants | 44 Participants |
| Sex: Female, Male Male | 27 Participants | 5 Participants | 2 Participants | 5 Participants | 13 Participants | 7 Participants | 9 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 6 | 0 / 3 | 0 / 6 | 0 / 3 | 0 / 7 | 0 / 26 | 0 / 25 | 0 / 5 | 0 / 11 | 0 / 5 | 0 / 12 |
| other Total, other adverse events | 2 / 3 | 6 / 6 | 3 / 3 | 5 / 6 | 3 / 3 | 7 / 7 | 23 / 26 | 22 / 25 | 4 / 5 | 10 / 11 | 2 / 5 | 10 / 12 |
| serious Total, serious adverse events | 0 / 3 | 0 / 6 | 0 / 3 | 0 / 6 | 0 / 3 | 1 / 7 | 1 / 26 | 0 / 25 | 0 / 5 | 0 / 11 | 0 / 5 | 0 / 12 |
Outcome results
Primary
Change From Baseline in Body Weight to the EOT (Cohort 4)
Time frame: Baseline (Day 1) and EOT (Day 42)
Population: Intent-to-treat (ITT) population included all participants who were randomized and received any study drug and analyzed according to the initial randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 4: Placebo | Change From Baseline in Body Weight to the EOT (Cohort 4) | -1.71 Kilograms (Kg) | Standard Deviation 2.1 |
| Cohort 4: MEDI0382 200 mcg | Change From Baseline in Body Weight to the EOT (Cohort 4) | -3.83 Kilograms (Kg) | Standard Deviation 2.09 |
p-value: 0.0008ANCOVA
Primary
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)
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 4: Placebo | 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) | -9.24 Percent change | Standard Deviation 12.3 |
| Cohort 4: MEDI0382 200 mcg | 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) | -33.81 Percent change | Standard Deviation 18.62 |
p-value: <0.0001ANCOVA
Secondary
Accumulation Ratio (Rac) of MEDI0382 (Cohorts 1, 2, and 3)
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort 4: Placebo | Accumulation Ratio (Rac) of MEDI0382 (Cohorts 1, 2, and 3) | Day 1 | NA Ratio |
| Cohort 4: Placebo | Accumulation Ratio (Rac) of MEDI0382 (Cohorts 1, 2, and 3) | Day 7 | 1.3 Ratio |
| Cohort 4: MEDI0382 200 mcg | Accumulation Ratio (Rac) of MEDI0382 (Cohorts 1, 2, and 3) | Day 5 | NA Ratio |
| Cohort 4: MEDI0382 200 mcg | Accumulation Ratio (Rac) of MEDI0382 (Cohorts 1, 2, and 3) | Day 11 | 1.1 Ratio |
| Cohort 2: Placebo | Accumulation Ratio (Rac) of MEDI0382 (Cohorts 1, 2, and 3) | Day 9 | NA Ratio |
| Cohort 2: Placebo | Accumulation Ratio (Rac) of MEDI0382 (Cohorts 1, 2, and 3) | Day 15 | 1.3 Ratio |
Secondary
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)
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort 4: Placebo | 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) | Day 1 | 82.21 ng*hr/mL |
| Cohort 4: Placebo | 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) | Day 7 | 107.01 ng*hr/mL |
| Cohort 4: MEDI0382 200 mcg | 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) | Day 5 | 174.58 ng*hr/mL |
| Cohort 4: MEDI0382 200 mcg | 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) | Day 11 | 157.31 ng*hr/mL |
| Cohort 2: Placebo | 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) | Day 15 | 195.40 ng*hr/mL |
| Cohort 2: Placebo | 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) | Day 9 | 194.78 ng*hr/mL |
| Cohort 2: MEDI0382 150 mcg | 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) | Day 41 | 199.10 ng*hr/mL |
| Cohort 2: MEDI0382 150 mcg | 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) | Day 9 | 164.05 ng*hr/mL |
| Cohort 3: Placebo | 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) | Day 16 | 261.90 ng*hr/mL |
| Cohort 3: Placebo | 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) | Day 22 | 254.35 ng*hr/mL |
| Cohort 3: MEDI0382 200 mcg | 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) | Day 17 | 246.06 ng*hr/mL |
| Cohort 3: MEDI0382 200 mcg | 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) | Day 11 | 275.29 ng*hr/mL |
Secondary
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort 4: Placebo | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 7 | 184.68 ng*hr/mL |
| Cohort 4: Placebo | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 1 | 103.46 ng*hr/mL |
| Cohort 4: MEDI0382 200 mcg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 11 | 215.80 ng*hr/mL |
| Cohort 4: MEDI0382 200 mcg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 5 | 207.15 ng*hr/mL |
| Cohort 2: Placebo | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 9 | 242.60 ng*hr/mL |
| Cohort 2: Placebo | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 15 | 271.84 ng*hr/mL |
| Cohort 2: MEDI0382 150 mcg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 41 | 262.17 ng*hr/mL |
| Cohort 2: MEDI0382 150 mcg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 9 | 238.22 ng*hr/mL |
| Cohort 3: Placebo | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 16 | 317.93 ng*hr/mL |
| Cohort 3: Placebo | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 22 | 294.60 ng*hr/mL |
| Cohort 3: MEDI0382 200 mcg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 17 | 327.28 ng*hr/mL |
Secondary
Change From Baseline in Body Weight to the EOT (Cohorts 1, 2, 3, 5, and 6)
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 4: Placebo | Change From Baseline in Body Weight to the EOT (Cohorts 1, 2, 3, 5, and 6) | -1.20 Kg | Standard Deviation 0.44 |
| Cohort 4: MEDI0382 200 mcg | Change From Baseline in Body Weight to the EOT (Cohorts 1, 2, 3, 5, and 6) | -2.32 Kg | Standard Deviation 1.29 |
| Cohort 2: Placebo | Change From Baseline in Body Weight to the EOT (Cohorts 1, 2, 3, 5, and 6) | -1.00 Kg | Standard Deviation 1.13 |
| Cohort 2: MEDI0382 150 mcg | Change From Baseline in Body Weight to the EOT (Cohorts 1, 2, 3, 5, and 6) | -1.52 Kg | Standard Deviation 0.57 |
| Cohort 3: Placebo | Change From Baseline in Body Weight to the EOT (Cohorts 1, 2, 3, 5, and 6) | -2.90 Kg | Standard Deviation 1.05 |
| Cohort 3: MEDI0382 200 mcg | Change From Baseline in Body Weight to the EOT (Cohorts 1, 2, 3, 5, and 6) | -4.63 Kg | Standard Deviation 1.98 |
| Cohort 5: Placebo | Change From Baseline in Body Weight to the EOT (Cohorts 1, 2, 3, 5, and 6) | -0.98 Kg | Standard Deviation 2.12 |
| Cohort 5: MEDI0382 300 mcg | Change From Baseline in Body Weight to the EOT (Cohorts 1, 2, 3, 5, and 6) | -3.26 Kg | Standard Deviation 1.99 |
| Cohort 6: Placebo | Change From Baseline in Body Weight to the EOT (Cohorts 1, 2, 3, 5, and 6) | -0.94 Kg | Standard Deviation 3.09 |
| Cohort 6: MEDI0382 300 mcg | Change From Baseline in Body Weight to the EOT (Cohorts 1, 2, 3, 5, and 6) | -2.04 Kg | Standard Deviation 1.52 |
Secondary
Change From Baseline in Fasting Glucose Prior to MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 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).
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 4: Placebo | Change From Baseline in Fasting Glucose Prior to MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6) | -32.44 mg/dL | Standard Deviation 17.19 |
| Cohort 4: MEDI0382 200 mcg | Change From Baseline in Fasting Glucose Prior to MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6) | -74.48 mg/dL | Standard Deviation 24.59 |
| Cohort 2: Placebo | Change From Baseline in Fasting Glucose Prior to MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6) | -49.86 mg/dL | Standard Deviation 23.24 |
| Cohort 2: MEDI0382 150 mcg | Change From Baseline in Fasting Glucose Prior to MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6) | -54.06 mg/dL | Standard Deviation 19.51 |
| Cohort 3: Placebo | Change From Baseline in Fasting Glucose Prior to MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6) | -4.20 mg/dL | Standard Deviation 33.73 |
| Cohort 3: MEDI0382 200 mcg | Change From Baseline in Fasting Glucose Prior to MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6) | -63.67 mg/dL | Standard Deviation 11.93 |
| Cohort 5: Placebo | Change From Baseline in Fasting Glucose Prior to MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6) | -18.52 mg/dL | Standard Deviation 18.88 |
| Cohort 5: MEDI0382 300 mcg | Change From Baseline in Fasting Glucose Prior to MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6) | -50.62 mg/dL | Standard Deviation 33.61 |
| Cohort 6: Placebo | Change From Baseline in Fasting Glucose Prior to MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6) | -32.08 mg/dL | Standard Deviation 17.49 |
| Cohort 6: MEDI0382 300 mcg | Change From Baseline in Fasting Glucose Prior to MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6) | -54.42 mg/dL | Standard Deviation 19.75 |
| Cohort 6: Placebo | Change From Baseline in Fasting Glucose Prior to MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6) | -16.58 mg/dL | Standard Deviation 12.45 |
| Cohort 6: MEDI0382 300 mcg | Change From Baseline in Fasting Glucose Prior to MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6) | -55.21 mg/dL | Standard Deviation 31.13 |
Secondary
Change From Baseline in Fructosamine to the EOT (Cohorts 4, 5, and 6)
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 4: Placebo | Change From Baseline in Fructosamine to the EOT (Cohorts 4, 5, and 6) | -33.7 micromol/L | Standard Deviation 44.6 |
| Cohort 4: MEDI0382 200 mcg | Change From Baseline in Fructosamine to the EOT (Cohorts 4, 5, and 6) | -67.9 micromol/L | Standard Deviation 44.4 |
| Cohort 2: Placebo | Change From Baseline in Fructosamine to the EOT (Cohorts 4, 5, and 6) | -27.8 micromol/L | Standard Deviation 25.8 |
| Cohort 2: MEDI0382 150 mcg | Change From Baseline in Fructosamine to the EOT (Cohorts 4, 5, and 6) | -47.4 micromol/L | Standard Deviation 15.7 |
| Cohort 3: Placebo | Change From Baseline in Fructosamine to the EOT (Cohorts 4, 5, and 6) | -48.8 micromol/L | Standard Deviation 43.7 |
| Cohort 3: MEDI0382 200 mcg | Change From Baseline in Fructosamine to the EOT (Cohorts 4, 5, and 6) | -47.5 micromol/L | Standard Deviation 55.3 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort 4: Placebo | Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 1 | 4.97 ng/mL |
| Cohort 4: Placebo | Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 7 | 6.26 ng/mL |
| Cohort 4: MEDI0382 200 mcg | Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 5 | 9.66 ng/mL |
| Cohort 4: MEDI0382 200 mcg | Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 11 | 9.57 ng/mL |
| Cohort 2: Placebo | Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 15 | 10.97 ng/mL |
| Cohort 2: Placebo | Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 9 | 10.57 ng/mL |
| Cohort 2: MEDI0382 150 mcg | Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 41 | 13.42 ng/mL |
| Cohort 2: MEDI0382 150 mcg | Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 9 | 11.64 ng/mL |
| Cohort 3: Placebo | Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 16 | 17.65 ng/mL |
| Cohort 3: Placebo | Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 22 | 15.77 ng/mL |
| Cohort 3: MEDI0382 200 mcg | Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 17 | 15.55 ng/mL |
| Cohort 3: MEDI0382 200 mcg | Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 11 | 13.69 ng/mL |
Secondary
Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort 4: Placebo | Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 1 | 0.705 ng/mL |
| Cohort 4: Placebo | Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 7 | 2.372 ng/mL |
| Cohort 4: MEDI0382 200 mcg | Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 5 | 2.685 ng/mL |
| Cohort 4: MEDI0382 200 mcg | Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 11 | 3.59 ng/mL |
| Cohort 2: Placebo | Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 15 | 4.973 ng/mL |
| Cohort 2: Placebo | Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 9 | 3.521 ng/mL |
| Cohort 2: MEDI0382 150 mcg | Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 41 | 3.38 ng/mL |
| Cohort 2: MEDI0382 150 mcg | Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 9 | 2.635 ng/mL |
| Cohort 3: Placebo | Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 16 | 4.062 ng/mL |
| Cohort 3: Placebo | Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 22 | 5.21 ng/mL |
| Cohort 3: MEDI0382 200 mcg | Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 17 | 4.766 ng/mL |
| Cohort 3: MEDI0382 200 mcg | Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 11 | 3.586 ng/mL |
Secondary
Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs
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])
Population: ATP included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 4: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Sinus tachycardia | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block first degree | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block second degree | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular extrasystoles | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular extrasystoles | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Extrasystoles | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Arrhythmia | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrial fibrillation | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular tachycardia | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular tachycardia | 1 Participants |
| Cohort 4: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Electrocardiogram ST segment depression | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Tachycardia | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Arrhythmia | 1 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrial fibrillation | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block first degree | 1 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Extrasystoles | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block second degree | 1 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular extrasystoles | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Tachycardia | 1 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular extrasystoles | 1 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular tachycardia | 1 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Electrocardiogram ST segment depression | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Sinus tachycardia | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular tachycardia | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Extrasystoles | 1 Participants |
| Cohort 2: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Sinus tachycardia | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular tachycardia | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrial fibrillation | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Arrhythmia | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular extrasystoles | 1 Participants |
| Cohort 2: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block first degree | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Tachycardia | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block second degree | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Electrocardiogram ST segment depression | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular tachycardia | 1 Participants |
| Cohort 2: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular extrasystoles | 0 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Arrhythmia | 0 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block second degree | 0 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular extrasystoles | 0 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Electrocardiogram ST segment depression | 0 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block first degree | 0 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Extrasystoles | 0 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular extrasystoles | 1 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular tachycardia | 0 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Sinus tachycardia | 0 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Tachycardia | 1 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrial fibrillation | 0 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular tachycardia | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular extrasystoles | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Arrhythmia | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Extrasystoles | 1 Participants |
| Cohort 3: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular extrasystoles | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Sinus tachycardia | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular tachycardia | 1 Participants |
| Cohort 3: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Tachycardia | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular tachycardia | 1 Participants |
| Cohort 3: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Electrocardiogram ST segment depression | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block second degree | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block first degree | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrial fibrillation | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Arrhythmia | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block second degree | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular tachycardia | 1 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular extrasystoles | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrial fibrillation | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Electrocardiogram ST segment depression | 1 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular extrasystoles | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular tachycardia | 1 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Sinus tachycardia | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Extrasystoles | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block first degree | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Tachycardia | 1 Participants |
| Cohort 5: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular extrasystoles | 1 Participants |
| Cohort 5: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Arrhythmia | 0 Participants |
| Cohort 5: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrial fibrillation | 0 Participants |
| Cohort 5: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block first degree | 0 Participants |
| Cohort 5: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block second degree | 0 Participants |
| Cohort 5: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Electrocardiogram ST segment depression | 0 Participants |
| Cohort 5: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Extrasystoles | 0 Participants |
| Cohort 5: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Sinus tachycardia | 0 Participants |
| Cohort 5: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular tachycardia | 0 Participants |
| Cohort 5: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Tachycardia | 0 Participants |
| Cohort 5: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular extrasystoles | 1 Participants |
| Cohort 5: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular tachycardia | 0 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block second degree | 0 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Arrhythmia | 0 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular extrasystoles | 0 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Electrocardiogram ST segment depression | 0 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular extrasystoles | 1 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrial fibrillation | 1 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Tachycardia | 0 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular tachycardia | 0 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular tachycardia | 0 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Extrasystoles | 0 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Sinus tachycardia | 1 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block first degree | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular extrasystoles | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Tachycardia | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block first degree | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular extrasystoles | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Arrhythmia | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block second degree | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Sinus tachycardia | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Electrocardiogram ST segment depression | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular tachycardia | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular tachycardia | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Extrasystoles | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrial fibrillation | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular extrasystoles | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Extrasystoles | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular extrasystoles | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Electrocardiogram ST segment depression | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular tachycardia | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block first degree | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular tachycardia | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Tachycardia | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrial fibrillation | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block second degree | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Arrhythmia | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Sinus tachycardia | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular tachycardia | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrial fibrillation | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Arrhythmia | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Sinus tachycardia | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular extrasystoles | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Electrocardiogram ST segment depression | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular tachycardia | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block first degree | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular extrasystoles | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Extrasystoles | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Tachycardia | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block second degree | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Tachycardia | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrial fibrillation | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Extrasystoles | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block second degree | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular extrasystoles | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular extrasystoles | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Sinus tachycardia | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Arrhythmia | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Electrocardiogram ST segment depression | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Ventricular tachycardia | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Atrioventricular block first degree | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs | Supraventricular tachycardia | 0 Participants |
Secondary
Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs
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])
Population: ATP included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 4: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | C-reactive protein increased | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypoglycemia | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Chromaturia | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypokalemia | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Lipase increased | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Lipase increased | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Chromaturia | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | C-reactive protein increased | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypokalemia | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypoglycemia | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Chromaturia | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Lipase increased | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypoglycemia | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypokalemia | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | C-reactive protein increased | 0 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypokalemia | 0 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Lipase increased | 1 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | C-reactive protein increased | 0 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypoglycemia | 0 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Chromaturia | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | C-reactive protein increased | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Lipase increased | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Chromaturia | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypokalemia | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypoglycemia | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypoglycemia | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypokalemia | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Chromaturia | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Lipase increased | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | C-reactive protein increased | 1 Participants |
| Cohort 5: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Lipase increased | 0 Participants |
| Cohort 5: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypokalemia | 1 Participants |
| Cohort 5: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | C-reactive protein increased | 0 Participants |
| Cohort 5: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypoglycemia | 0 Participants |
| Cohort 5: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Chromaturia | 0 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Chromaturia | 1 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Lipase increased | 1 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypokalemia | 1 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | C-reactive protein increased | 0 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypoglycemia | 1 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Chromaturia | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypokalemia | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | C-reactive protein increased | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypoglycemia | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Lipase increased | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypoglycemia | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Lipase increased | 2 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypokalemia | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Chromaturia | 1 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | C-reactive protein increased | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypoglycemia | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypokalemia | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Chromaturia | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | C-reactive protein increased | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Lipase increased | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Chromaturia | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Lipase increased | 1 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypoglycemia | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | Hypokalemia | 1 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs | C-reactive protein increased | 0 Participants |
Secondary
Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs
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])
Population: ATP included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 4: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure diastolic increased | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure systolic increased | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Physical Examinations | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood Pressure increased | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure systolic increased | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood Pressure increased | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure diastolic increased | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Physical Examinations | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood Pressure increased | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure systolic increased | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure diastolic increased | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Physical Examinations | 0 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood Pressure increased | 0 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Physical Examinations | 0 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure systolic increased | 0 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure diastolic increased | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure systolic increased | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Physical Examinations | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure diastolic increased | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood Pressure increased | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood Pressure increased | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure systolic increased | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Physical Examinations | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure diastolic increased | 0 Participants |
| Cohort 5: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure diastolic increased | 0 Participants |
| Cohort 5: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood Pressure increased | 2 Participants |
| Cohort 5: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure systolic increased | 0 Participants |
| Cohort 5: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Physical Examinations | 0 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure systolic increased | 0 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood Pressure increased | 1 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Physical Examinations | 0 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure diastolic increased | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure diastolic increased | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Physical Examinations | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure systolic increased | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood Pressure increased | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood Pressure increased | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure diastolic increased | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure systolic increased | 1 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Physical Examinations | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure systolic increased | 1 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure diastolic increased | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood Pressure increased | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Physical Examinations | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood Pressure increased | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure diastolic increased | 1 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Blood pressure systolic increased | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs | Physical Examinations | 0 Participants |
Secondary
Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6)
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)
Population: ATP included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 4: Placebo | Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) | Day -1 | 2 Participants |
| Cohort 4: Placebo | Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) | Day 13 | 1 Participants |
| Cohort 4: Placebo | Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) | Day 20 | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) | Day 27 | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) | Day 34 | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) | Day 40 | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) | Day 40 | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) | Day 13 | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) | Day 20 | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) | Day 27 | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) | Day 34 | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) | Day -1 | 2 Participants |
| Cohort 2: Placebo | Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) | Days 7-14 post last dose of MEDI0382 | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) | Day -1 | 0 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) | Day -1 | 1 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) | Days 7-14 post last dose of MEDI0382 | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) | Day -1 | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) | Days 7-14 post last dose of MEDI0382 | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) | Days 7-14 post last dose of MEDI0382 | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) | Day -1 | 1 Participants |
Secondary
Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6)
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)
Population: ATP included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 4: Placebo | Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) | Day -1 | 1 Participants |
| Cohort 4: Placebo | Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) | Day 13 | 1 Participants |
| Cohort 4: Placebo | Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) | Day 20 | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) | Day 27 | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) | Day 34 | 0 Participants |
| Cohort 4: Placebo | Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) | Day 40 | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) | Day 40 | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) | Day 13 | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) | Day 20 | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) | Day 27 | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) | Day 34 | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) | Day -1 | 4 Participants |
| Cohort 2: Placebo | Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) | Days 7-14 post last dose of MEDI0382 | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) | Day -1 | 0 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) | Day -1 | 2 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) | Days 7-14 post last dose of MEDI0382 | 1 Participants |
| Cohort 3: Placebo | Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) | Day -1 | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) | Days 7-14 post last dose of MEDI0382 | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) | Days 7-14 post last dose of MEDI0382 | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) | Day -1 | 2 Participants |
Secondary
Number of Participants With Positive Anti-drug Antibodies to MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
Time frame: Day 1 up to 7-14 days post-last dose of MEDI0382 for all cohorts (Approximately 60 days)
Population: ATP included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 4: Placebo | Number of Participants With Positive Anti-drug Antibodies to MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Positive Anti-drug Antibodies to MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Positive Anti-drug Antibodies to MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | 1 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Positive Anti-drug Antibodies to MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Positive Anti-drug Antibodies to MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | 0 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Positive Anti-drug Antibodies to MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | 0 Participants |
| Cohort 5: Placebo | Number of Participants With Positive Anti-drug Antibodies to MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | 0 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Positive Anti-drug Antibodies to MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Positive Anti-drug Antibodies to MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Positive Anti-drug Antibodies to MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Positive Anti-drug Antibodies to MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Positive Anti-drug Antibodies to MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | 0 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
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])
Population: As-treated Population (ATP) included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 4: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 2 Participants |
| Cohort 4: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 6 Participants |
| Cohort 4: MEDI0382 200 mcg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 3 Participants |
| Cohort 2: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 5 Participants |
| Cohort 2: MEDI0382 150 mcg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Cohort 3: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 3 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 7 Participants |
| Cohort 3: MEDI0382 200 mcg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 1 Participants |
| Cohort 5: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 1 Participants |
| Cohort 5: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 23 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 22 Participants |
| Cohort 5: MEDI0382 300 mcg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 4 Participants |
| Cohort 6: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 10 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Cohort 6: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 2 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Cohort 6: MEDI0382 300 mcg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 10 Participants |
Secondary
Percent Change From Baseline in C-peptide AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 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).
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 4: Placebo | Percent Change From Baseline in C-peptide AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | 10.17 Percent change | Standard Deviation 5.05 |
| Cohort 4: MEDI0382 200 mcg | Percent Change From Baseline in C-peptide AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | -3.82 Percent change | Standard Deviation 21.29 |
| Cohort 2: Placebo | Percent Change From Baseline in C-peptide AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | -1.43 Percent change | Standard Deviation 6.02 |
| Cohort 2: MEDI0382 150 mcg | Percent Change From Baseline in C-peptide AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | 39.78 Percent change | Standard Deviation 32.88 |
| Cohort 3: Placebo | Percent Change From Baseline in C-peptide AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | 79.37 Percent change | Standard Deviation 91.56 |
| Cohort 3: MEDI0382 200 mcg | Percent Change From Baseline in C-peptide AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | -9.07 Percent change | Standard Deviation 27.27 |
| Cohort 5: Placebo | Percent Change From Baseline in C-peptide AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | 8.08 Percent change | Standard Deviation 32.12 |
| Cohort 5: MEDI0382 300 mcg | Percent Change From Baseline in C-peptide AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | 15.66 Percent change | Standard Deviation 42.35 |
Secondary
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)
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 4: Placebo | 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) | -21.80 Percent change | Standard Deviation 1.41 |
| Cohort 4: MEDI0382 200 mcg | 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) | -28.34 Percent change | Standard Deviation 13.52 |
| Cohort 2: Placebo | 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) | 0.80 Percent change | Standard Deviation 39.55 |
| Cohort 2: MEDI0382 150 mcg | 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) | -29.32 Percent change | Standard Deviation 17.24 |
| Cohort 3: Placebo | 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) | -13.80 Percent change | Standard Deviation 15.95 |
| Cohort 3: MEDI0382 200 mcg | 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) | -27.07 Percent change | Standard Deviation 10.82 |
| Cohort 5: Placebo | 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) | -1.06 Percent change | Standard Deviation 11.47 |
| Cohort 5: MEDI0382 300 mcg | 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) | -13.50 Percent change | Standard Deviation 18.19 |
| Cohort 6: Placebo | 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) | -4.20 Percent change | Standard Deviation 28.58 |
| Cohort 6: MEDI0382 300 mcg | 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) | -34.51 Percent change | Standard Deviation 11.25 |
| Cohort 6: Placebo | 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) | -10.10 Percent change | Standard Deviation 14.69 |
| Cohort 6: MEDI0382 300 mcg | 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) | -26.95 Percent change | Standard Deviation 9.45 |
Secondary
Percent Change From Baseline in Hemoglobin A1c (HbA1c) to the EOT (Cohorts 4, 5, and 6)
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 4: Placebo | Percent Change From Baseline in Hemoglobin A1c (HbA1c) to the EOT (Cohorts 4, 5, and 6) | -0.58 Percent change | Standard Deviation 0.3 |
| Cohort 4: MEDI0382 200 mcg | Percent Change From Baseline in Hemoglobin A1c (HbA1c) to the EOT (Cohorts 4, 5, and 6) | -0.92 Percent change | Standard Deviation 0.41 |
| Cohort 2: Placebo | Percent Change From Baseline in Hemoglobin A1c (HbA1c) to the EOT (Cohorts 4, 5, and 6) | -0.10 Percent change | Standard Deviation 0.29 |
| Cohort 2: MEDI0382 150 mcg | Percent Change From Baseline in Hemoglobin A1c (HbA1c) to the EOT (Cohorts 4, 5, and 6) | -0.55 Percent change | Standard Deviation 0.35 |
| Cohort 3: Placebo | Percent Change From Baseline in Hemoglobin A1c (HbA1c) to the EOT (Cohorts 4, 5, and 6) | -0.18 Percent change | Standard Deviation 0.19 |
| Cohort 3: MEDI0382 200 mcg | Percent Change From Baseline in Hemoglobin A1c (HbA1c) to the EOT (Cohorts 4, 5, and 6) | -0.42 Percent change | Standard Deviation 0.27 |
Secondary
Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 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).
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 4: Placebo | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | Glucagon: Change at EOT | -13.85 Percent change | Standard Deviation 18.6 |
| Cohort 4: Placebo | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GLP-1, Inactive: Change at EOT | -20.30 Percent change | — |
| Cohort 4: Placebo | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GLP-1, Active: Change at EOT | 8.30 Percent change | Standard Deviation 13.15 |
| Cohort 4: Placebo | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GIP: Change at EOT | 18.00 Percent change | Standard Deviation 2.83 |
| Cohort 4: MEDI0382 200 mcg | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GLP-1, Active: Change at EOT | -33.67 Percent change | Standard Deviation 16.84 |
| Cohort 4: MEDI0382 200 mcg | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GLP-1, Inactive: Change at EOT | 0.70 Percent change | — |
| Cohort 4: MEDI0382 200 mcg | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GIP: Change at EOT | -46.50 Percent change | Standard Deviation 14.85 |
| Cohort 4: MEDI0382 200 mcg | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | Glucagon: Change at EOT | -20.25 Percent change | Standard Deviation 25.45 |
| Cohort 2: Placebo | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GLP-1, Active: Change at EOT | -10.40 Percent change | Standard Deviation 10.47 |
| Cohort 2: Placebo | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GIP: Change at EOT | 4.10 Percent change | Standard Deviation 24.61 |
| Cohort 2: Placebo | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | Glucagon: Change at EOT | -17.53 Percent change | Standard Deviation 19.46 |
| Cohort 2: Placebo | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GLP-1, Inactive: Change at EOT | -22.90 Percent change | — |
| Cohort 2: MEDI0382 150 mcg | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | Glucagon: Change at EOT | -38.12 Percent change | Standard Deviation 16.33 |
| Cohort 2: MEDI0382 150 mcg | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GLP-1, Inactive: Change at EOT | -10.93 Percent change | Standard Deviation 22.36 |
| Cohort 2: MEDI0382 150 mcg | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GIP: Change at EOT | -27.08 Percent change | Standard Deviation 25.03 |
| Cohort 2: MEDI0382 150 mcg | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GLP-1, Active: Change at EOT | -50.45 Percent change | Standard Deviation 12.3 |
| Cohort 3: Placebo | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GLP-1, Active: Change at EOT | -2.87 Percent change | Standard Deviation 20.32 |
| Cohort 3: Placebo | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GLP-1, Inactive: Change at EOT | 1.75 Percent change | Standard Deviation 29.2 |
| Cohort 3: Placebo | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | Glucagon: Change at EOT | -18.73 Percent change | Standard Deviation 21.59 |
| Cohort 3: Placebo | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GIP: Change at EOT | -6.30 Percent change | Standard Deviation 7.35 |
| Cohort 3: MEDI0382 200 mcg | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GLP-1, Inactive: Change at EOT | -8.07 Percent change | Standard Deviation 11.3 |
| Cohort 3: MEDI0382 200 mcg | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GLP-1, Active: Change at EOT | -40.36 Percent change | Standard Deviation 26.9 |
| Cohort 3: MEDI0382 200 mcg | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | Glucagon: Change at EOT | -3.05 Percent change | Standard Deviation 36.56 |
| Cohort 3: MEDI0382 200 mcg | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GIP: Change at EOT | -21.34 Percent change | Standard Deviation 39.48 |
| Cohort 5: Placebo | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GLP-1, Inactive: Change at EOT | 3.99 Percent change | Standard Deviation 29.59 |
| Cohort 5: Placebo | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | Glucagon: Change at EOT | -1.76 Percent change | Standard Deviation 21.47 |
| Cohort 5: Placebo | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GLP-1, Active: Change at EOT | 1.63 Percent change | Standard Deviation 26.43 |
| Cohort 5: Placebo | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GIP: Change at EOT | -6.60 Percent change | Standard Deviation 19.43 |
| Cohort 5: MEDI0382 300 mcg | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GIP: Change at EOT | -37.38 Percent change | Standard Deviation 23.14 |
| Cohort 5: MEDI0382 300 mcg | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | Glucagon: Change at EOT | -30.17 Percent change | Standard Deviation 25.56 |
| Cohort 5: MEDI0382 300 mcg | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GLP-1, Inactive: Change at EOT | -28.85 Percent change | Standard Deviation 16.73 |
| Cohort 5: MEDI0382 300 mcg | Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | GLP-1, Active: Change at EOT | -49.73 Percent change | Standard Deviation 22.88 |
Secondary
Percent Change From Baseline in Insulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, 4, 5, and 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).
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 4: Placebo | Percent Change From Baseline in Insulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, 4, 5, and 6) | 10.83 Percent change | Standard Deviation 21.33 |
| Cohort 4: MEDI0382 200 mcg | Percent Change From Baseline in Insulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, 4, 5, and 6) | -9.37 Percent change | Standard Deviation 29.17 |
| Cohort 2: Placebo | Percent Change From Baseline in Insulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, 4, 5, and 6) | -3.67 Percent change | Standard Deviation 13.76 |
| Cohort 2: MEDI0382 150 mcg | Percent Change From Baseline in Insulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, 4, 5, and 6) | 36.32 Percent change | Standard Deviation 35.21 |
| Cohort 3: Placebo | Percent Change From Baseline in Insulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, 4, 5, and 6) | -20.43 Percent change | Standard Deviation 68.82 |
| Cohort 3: MEDI0382 200 mcg | Percent Change From Baseline in Insulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, 4, 5, and 6) | -17.47 Percent change | Standard Deviation 38.84 |
| Cohort 5: Placebo | Percent Change From Baseline in Insulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, 4, 5, and 6) | -8.63 Percent change | Standard Deviation 32.33 |
| Cohort 5: MEDI0382 300 mcg | Percent Change From Baseline in Insulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, 4, 5, and 6) | -1.17 Percent change | Standard Deviation 44.2 |
| Cohort 6: Placebo | Percent Change From Baseline in Insulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, 4, 5, and 6) | -17.70 Percent change | Standard Deviation 16.47 |
| Cohort 6: MEDI0382 300 mcg | Percent Change From Baseline in Insulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, 4, 5, and 6) | 1.01 Percent change | Standard Deviation 31 |
| Cohort 6: Placebo | Percent Change From Baseline in Insulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, 4, 5, and 6) | -8.18 Percent change | Standard Deviation 28.34 |
| Cohort 6: MEDI0382 300 mcg | Percent Change From Baseline in Insulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, 4, 5, and 6) | -7.72 Percent change | Standard Deviation 37.03 |
Secondary
Percent Change From Baseline in MMT Glucose AUC0-4h to the EOT (Cohorts 1, 2, 3, 5, and 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).
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 4: Placebo | Percent Change From Baseline in MMT Glucose AUC0-4h to the EOT (Cohorts 1, 2, 3, 5, and 6) | -14.60 Percent change | Standard Deviation 5.56 |
| Cohort 4: MEDI0382 200 mcg | Percent Change From Baseline in MMT Glucose AUC0-4h to the EOT (Cohorts 1, 2, 3, 5, and 6) | -41.80 Percent change | Standard Deviation 11.07 |
| Cohort 2: Placebo | Percent Change From Baseline in MMT Glucose AUC0-4h to the EOT (Cohorts 1, 2, 3, 5, and 6) | -15.07 Percent change | Standard Deviation 13.46 |
| Cohort 2: MEDI0382 150 mcg | Percent Change From Baseline in MMT Glucose AUC0-4h to the EOT (Cohorts 1, 2, 3, 5, and 6) | -36.73 Percent change | Standard Deviation 10.09 |
| Cohort 3: Placebo | Percent Change From Baseline in MMT Glucose AUC0-4h to the EOT (Cohorts 1, 2, 3, 5, and 6) | -0.47 Percent change | Standard Deviation 15.16 |
| Cohort 3: MEDI0382 200 mcg | Percent Change From Baseline in MMT Glucose AUC0-4h to the EOT (Cohorts 1, 2, 3, 5, and 6) | -39.58 Percent change | Standard Deviation 5.27 |
| Cohort 5: Placebo | Percent Change From Baseline in MMT Glucose AUC0-4h to the EOT (Cohorts 1, 2, 3, 5, and 6) | -14.52 Percent change | Standard Deviation 8.12 |
| Cohort 5: MEDI0382 300 mcg | Percent Change From Baseline in MMT Glucose AUC0-4h to the EOT (Cohorts 1, 2, 3, 5, and 6) | -41.66 Percent change | Standard Deviation 9.97 |
| Cohort 6: Placebo | Percent Change From Baseline in MMT Glucose AUC0-4h to the EOT (Cohorts 1, 2, 3, 5, and 6) | -4.80 Percent change | Standard Deviation 3.45 |
| Cohort 6: MEDI0382 300 mcg | Percent Change From Baseline in MMT Glucose AUC0-4h to the EOT (Cohorts 1, 2, 3, 5, and 6) | -38.19 Percent change | Standard Deviation 12.51 |
Secondary
Percent Change From Baseline in Proinsulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 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).
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 4: Placebo | Percent Change From Baseline in Proinsulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | -3.27 Percent change | Standard Deviation 38.92 |
| Cohort 4: MEDI0382 200 mcg | Percent Change From Baseline in Proinsulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | -52.10 Percent change | Standard Deviation 36.29 |
| Cohort 2: Placebo | Percent Change From Baseline in Proinsulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | -33.13 Percent change | Standard Deviation 40.07 |
| Cohort 2: MEDI0382 150 mcg | Percent Change From Baseline in Proinsulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | -36.77 Percent change | Standard Deviation 19.62 |
| Cohort 3: Placebo | Percent Change From Baseline in Proinsulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | 81.27 Percent change | Standard Deviation 77.21 |
| Cohort 3: MEDI0382 200 mcg | Percent Change From Baseline in Proinsulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | -54.13 Percent change | Standard Deviation 26.4 |
| Cohort 5: Placebo | Percent Change From Baseline in Proinsulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | -29.72 Percent change | Standard Deviation 31.13 |
| Cohort 5: MEDI0382 300 mcg | Percent Change From Baseline in Proinsulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) | -47.93 Percent change | Standard Deviation 22.12 |
Secondary
Terminal Elimination Half Life (t1/2) of MEDI0382 (Cohorts 1, 2, and 3)
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort 4: Placebo | Terminal Elimination Half Life (t1/2) of MEDI0382 (Cohorts 1, 2, and 3) | Day 1 | 8.5 hr |
| Cohort 4: Placebo | Terminal Elimination Half Life (t1/2) of MEDI0382 (Cohorts 1, 2, and 3) | Day 7 | 11.7 hr |
| Cohort 4: MEDI0382 200 mcg | Terminal Elimination Half Life (t1/2) of MEDI0382 (Cohorts 1, 2, and 3) | Day 5 | 10.3 hr |
| Cohort 4: MEDI0382 200 mcg | Terminal Elimination Half Life (t1/2) of MEDI0382 (Cohorts 1, 2, and 3) | Day 11 | 11.3 hr |
| Cohort 2: Placebo | Terminal Elimination Half Life (t1/2) of MEDI0382 (Cohorts 1, 2, and 3) | Day 9 | 8.3 hr |
| Cohort 2: Placebo | Terminal Elimination Half Life (t1/2) of MEDI0382 (Cohorts 1, 2, and 3) | Day 15 | 11.3 hr |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 4: Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 7 | 6 hr |
| Cohort 4: Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 1 | 8 hr |
| Cohort 4: MEDI0382 200 mcg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 11 | 6 hr |
| Cohort 4: MEDI0382 200 mcg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 5 | 6 hr |
| Cohort 2: Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 15 | 6 hr |
| Cohort 2: Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 9 | 6 hr |
| Cohort 2: MEDI0382 150 mcg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 41 | 4 hr |
| Cohort 2: MEDI0382 150 mcg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 9 | 4 hr |
| Cohort 3: Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 22 | 4 hr |
| Cohort 3: Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 16 | 4 hr |
| Cohort 3: MEDI0382 200 mcg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 11 | 6 hr |
| Cohort 3: MEDI0382 200 mcg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) | Day 17 | 4 hr |