A Study to Investigate Different Doses of 0382 in Overweight and Obese Subjects With Type 2 Diabetes Mellitus.
Study Details
Study Description
Brief Summary
A Phase 2 study with two cohorts of differing doses designed to evaluate the efficacy, safety and pharmacokinetics (PK) of MEDI0382 in patients with Type 2 Diabetes Mellitus (T2DM). Approximately 63 subjects will be enrolled across two cohorts.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This is a randomised, double-blind, placebo-controlled study designed to evaluate the efficacy, safety, tolerability, and pharmacokinetics of different doses of MEDI0382 administered as multiple SC doses to subjects with T2DM. Approximately 63 subjects will be enrolled across two cohorts.
For cohort 1, sufficient subjects will be invited to participate in the study such that a maximum of 39 subjects will complete dosing. Subjects in cohort 1 will be randomised using a ratio of 2:1 to one of 2 treatment arms to receive either MEDI0382 or placebo. A maximum of 26 will complete dosing in the active arm and 13 will complete dosing in the placebo arm.
For cohort 2, sufficient subjects will be invited to participate in the study such that a maximum of 24 subjects will complete dosing. Subjects in cohort 2 will be randomised using a ratio of 3:1 to receive either MEDI0382 or placebo. A maximum of 18 will complete dosing in the active arm and 6 will complete dosing in the placebo arm.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Cohort 1 Participants will receive placebo matching with MEDI0382 subcutaneously once daily for 49 days. |
Drug: Placebo
Placebo will be administered subcutaneously once daily for 49 days.
|
| Experimental: MEDI0382 Cohort 1 Participants will receive subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days |
Drug: MEDI0382
MEDI0382 will be administered subcutaneously once daily for 49 days.
|
| Placebo Comparator: PLacebo Cohort 2 Participants will receive placebo matching with MEDI0382 subcutaneously once daily for 49 days. |
Drug: Placebo
Placebo will be administered subcutaneously once daily for 49 days.
|
| Experimental: MEDI0382 Cohort 2 Participants will receive subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 14 days, followed by Dose 2 for 14 days, Dose 3 for 14 days, and Dose 4 for 7 days. |
Drug: MEDI0382
MEDI0382 will be administered subcutaneously once daily for 49 days.
|
Outcome Measures
Primary Outcome Measures
- Cohort 1: Percent Change From Baseline in Plasma Glucose Area Under the Concentration-time Curve From Time 0 to 4 Hours (AUC0-4h) by Mixed-meal Tolerance Test (MMTT) to Day 49 [Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised liquid meal]
The MMTT test involved the consumption of a standardised liquid meal within 5 minutes and timed serial blood samples obtained for the measurement of glucose and parameters related to glucose metabolism through 240 minutes after consumption of the standardised meal (with no additional food intake during this time). The percent change in the MMTT plasma glucose AUC 0-4h from the baseline (Day -1) to Day 49 is reported.
- Cohort 1: Percent Change From Baseline in Body Weight to Day 50 [Day 1 through Day 50]
The percent change in body weight from baseline to Day 50 is reported.
Secondary Outcome Measures
- Cohort 1: Change From Baseline in Glycated Haemoglobin (HbA1c) to Day 49 [Baseline (Day -1) through Day 49]
The change from baseline in Glycated haemoglobin (HbA1c) to Day 49 is reported.
- Cohort 1: Change From Baseline in Fasting Plasma Glucose to Day 49 [Baseline (Day -1) through Day 49]
The changes in the fasting plasma glucose level during the study period from baseline to Day 49 is reported.
- Cohort 1: Change From Baseline in Body Weight to Day 50 [Day 1 through Day 50]
The changes in the body weight during the study period from baseline to Day 50 is reported.
- Cohort 1: Percentage of Participants Achieving Greater Than or Equal to 5% Body Weight Loss From Baseline to Day 50 [Day 1 through Day 50]
Participants achieving greater than or equal to 5% body weight loss from baseline to Day 50 is reported.
- Cohort 1 and Cohort 2: Percent Change From Baseline in MMTT Plasma Glucose AUC 0-4h to Day 7 [Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised liquid meal]
The MMTT test involved the consumption of a standardised liquid meal within 5 minutes and timed serial blood samples obtained for the measurement of glucose and parameters related to glucose metabolism through 240 minutes after consumption of the standardised meal (with no additional food intake during this time). The percent change in the MMTT plasma glucose AUC 0-4h from the baseline (Day -1) evaluation to Day 7 is reported.
- Cohort 1 and Cohort 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days)]
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are the events between first doses of study drug through 7 to 14 days after the last dose of study drug (approximately 64 days).
- Cohort 1 and Cohort 2: Number of Participants With Abnormal Vital Signs Reported as TEAEs [From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days)]
Treatment-emergent adverse events observed in participants with clinically significant vital signs abnormalities are reported. Vital sign parameters included blood pressure, heart rate, body temperature, and respiration rate.
- Cohort 1 and Cohort 2: Number of Participants With Abnormal Electrocardiogram Reported as TEAEs [From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days)]
Treatment-emergent adverse events observed in participants with clinically significant ECG abnormalities are reported.
- Cohort 1 and Cohort 2: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs [From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days)]
An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator as medically significant was reported as an AE. Laboratory evaluations included haematology, serum chemistry, and urinalysis.
- Cohort 1 and Cohort 2: Number of Participants With Injection Site Erythema [From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days)]
The injection site reactions observed during study visits were reported. Injection site reactions included (but are not limited to) local erythema, pain, tenderness, induration, swelling, pruritus, ulceration, and pigmentation.
- Cohort 1: Area Under the Concentration-time Curve During the Dosing Interval (AUCt) of MEDI0382 [Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49]
The area under the concentration-time curve during the dosing interval of MEDI0382 is reported.
- Cohort 2: Area Under the Concentration-time Curve During the Dosing Interval (AUCt) of MEDI0382 [Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14]
The area under the concentration-time curve during the dosing interval of MEDI0382 is reported.
- Cohort 1: Maximum Observed Concentration (Cmax) of MEDI0382 [Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49]
The maximum observed concentration of MEDI0382 is reported.
- Cohort 2: Maximum Observed Concentration (Cmax) of MEDI0382 [Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14]
The maximum observed concentration of MEDI0382 is reported.
- Cohort 1: Time to Reach Maximum Observed Concentration (Tmax) of MEDI0382 [Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49]
The time to reach the maximum observed concentration of MEDI0382 is reported.
- Cohort 2: Time to Reach Maximum Observed Concentration (Tmax) of MEDI0382 [Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14]
The time to reach the maximum observed concentration of MEDI0382 is reported.
- Cohort 1: Terminal Half Life (t1/2) of MEDI0382 [Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49]
The t1/2 is the time measured for the concentration to decrease by one half after the dose of MEDI0382.
- Cohort 2: Terminal Half Life (t1/2) of MEDI0382 [Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14]
The t1/2 is the time measured for the concentration to decrease by one half after the dose of MEDI0382.
- Cohort 1: Accumulation Ratio (Racc) of MEDI0382 [Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49]
The Racc was calculated using the AUC method which account for the overall exposure measured using the specified time points on Day 22 and Day 49. Racc was calculated using the formula, Racc of Day 49 = AUCt of Day 49/AUCt of Day 22.
- Cohort 2: Accumulation Ratio of MEDI0382 [Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14]
The Racc was calculated using the AUC method which account for the overall exposure measured using the specified time points on Day 1, Day 7 and Day 14. Racc was calculated using the formulas: Racc of Day 7 = AUCt of Day 7/AUCt of Day 1; Racc of Day 14 = AUCt of Day 14/AUCt of Day 1.
- Cohort 1: Trough Plasma Concentration (Ctrough) of MEDI0382 [Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49]
Trough plasma concentration is the measured concentration from the plasma concentration-time data at the end of a dosing interval at steady state.
- Cohort 2: Trough Plasma Concentration (Ctrough) of MEDI0382 [Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14]
Trough plasma concentration is the measured concentration from the plasma concentration time data at the end of a dosing interval at steady state.
- Cohort 1 and Cohort 2: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0382 [Baseline (Day 1), Day 29, Day 50, and Follow-up Visit 2 (28 days after the last dose [approximately 64 days])]
Participants with positive serum antibodies to MEDI0382 are reported.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male and female subjects aged ≥ 18 years at screening
-
Provision of signed and dated written informed consent
-
BMI between 27 and 40 kg/m2
-
HbA1c range of 6.5% to 8.5%
-
Diagnosed with T2DM with glucose control managed with metformin monotherapy where no significant dose change (increase or decrease ≥ 500 mg/day) has occurred in the 3 months prior to screening
-
Subjects prescribed oral dual therapy with a dipeptidyl peptidase-4 inhibitor, sulphonylurea, glitinide, or a sodium-glucose co-transporter 2 inhibitor in addition to metformin at screening may be eligible to enter the study following a 4-week washout period
-
Female subjects of childbearing potential must have a negative pregnancy test at screening and randomisation, and must not be lactating
-
Females of childbearing potential who are sexually active with a nonsterilised male partner must use at least one highly effective method of contraception from screening and must agree to continue using such precautions through to the end of the study. It is strongly recommended for the male partner of a female subject to also use male condom plus spermicide throughout this period. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.
Exclusion Criteria:
-
History of, or any existing condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product, put the subject at risk, influence the subject's ability to participate or affect the interpretation of the results of the study and/or any subject unable or unwilling to follow study procedures
-
Concurrent participation in another study of any kind and repeat randomisation in this study is prohibited
-
Severe allergy/hypersensitivity to any of the proposed study treatments
-
Symptoms of acutely decompensated blood glucose control (eg, thirst, polyuria, weight loss), a history of type 1 diabetes mellitus or diabetic ketoacidosis, or if the subject has been treated with daily SC insulin within 90 days prior to screening
-
Significant inflammatory bowel disease, gastroparesis, or other severe disease or surgery affecting the upper GI tract (including weight-reducing surgery and procedures) which may affect gastric emptying or could affect the interpretation of safety and tolerability data
-
Significant hepatic disease (except for non-alcoholic steatohepatitis or non-alcoholic fatty liver disease without portal hypertension or cirrhosis) and/or subjects with any of the following results at screening:
-
Aspartate transaminase (AST) ≥ 3 × upper limit of normal (ULN)
-
Alanine transaminase (ALT) ≥ 3 × ULN
-
Total bilirubin ≥ 2 × ULN
-
Impaired renal function defined as estimated glomerular filtration rate (GFR) < 60 mL/minute/1.73 m2 at screening (GFR estimated according to Modification of Diet in Renal Disease [MDRD] using the isotope dilution mass spectrometry [IDMS] traceable MDRD Study Equation [SI units])
-
Poorly controlled hypertension defined as:
-
Systolic BP > 160 mm Hg
-
Diastolic BP ≥ 95 mm Hg after 10 minutes of seated rest and confirmed by repeated measurement at screening.
-
Unstable angina pectoris, myocardial infarction, transient ischemic attack or stroke within 3 months prior to screening, or subjects who have undergone percutaneous coronary intervention or a coronary artery bypass graft within the past 6 months or who are due to undergo these procedures at the time of screening
-
Severe congestive heart failure (New York Heart Association Class III or IV)
-
Basal calcitonin level > 50 ng/L at screening or history/family history of medullary thyroid carcinoma or multiple endocrine neoplasia
-
Haemoglobinopathy, haemolytic anemia, or chronic anaemia (haemoglobin concentration < 11.5 g/dL [115 g/L] for males, < 10.5 g/dL [105 g/L] for females) at screening or any other condition known to interfere with interpretation of HbA1c measurement
-
History of neoplastic disease within 5 years prior to screening, except for adequately treated basal cell, squamous cell skin cancer, or in situ cervical cancer
-
Any positive results for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody, and human immunodeficiency virus (HIV) antibody
-
History of substance dependence, alcohol abuse, or excessive alcohol intake (defined as an average weekly intake of > 21 alcoholic drinks for men or > 10 alcoholic drinks for women) within 3 years prior to screening, and/or a positive screen for drugs of abuse or alcohol at screening or on admission to the study unit. Subjects who use tricyclic antidepressants or benzodiazepines for an established clinical indication may be permitted to enter the study based upon the judgement of the investigator.
-
Involvement of any AstraZeneca, MedImmune, contract research organization, or study site employee or their close relatives
-
History of acute or chronic pancreatitis or other diseases of the pancreas
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Berlin | Germany | 10117 | |
| 2 | Research Site | Magdeburg | Germany | 39120 | |
| 3 | Research Site | Mainz | Germany | 55116 | |
| 4 | Research Site | Neu-Ulm | Germany | 89231 | |
| 5 | Research Site | Neuss | Germany | 41460 |
Sponsors and Collaborators
- MedImmune LLC
Investigators
- Principal Investigator: Tim Heise, MD, Profil Institut für Stoffwechselforschung GmbH
Study Documents (Full-Text)
More Information
Additional Information:
- D5670C00011_protocol_amendment_2_ct
- D5670C00011_Statistical_Analysis_Plan
- A publication on the website: The Journal of Clinical Endocrinology & Metabolism
Publications
None provided.- D5670C00011
Study Results
Participant Flow
| Recruitment Details | The study was conducted across 5 sites in Germany between 04Sep2017 and 23Jan2018. |
|---|---|
| Pre-assignment Detail | A total of 120 participants consented to participate in the study. Of which 55 were screen failures; 65 participants were randomised (46 to MEDI0382 and 19 to placebo). |
| Arm/Group Title | Placebo Cohort 1 | MEDI0382 Cohort 1 | Placebo Cohort 2 | MEDI0382 Cohort 2 |
|---|---|---|---|---|
| Arm/Group Description | Participants received placebo matching with MEDI0382 subcutaneously (SC) once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. | Participants received placebo matching with MEDI0382 SC once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 14 days, followed by Dose 2 for 14 days, Dose 3 for 14 days, and Dose 4 for 7 days. |
| Period Title: Overall Study | ||||
| STARTED | 13 | 26 | 6 | 20 |
| COMPLETED | 13 | 25 | 6 | 18 |
| NOT COMPLETED | 0 | 1 | 0 | 2 |
Baseline Characteristics
| Arm/Group Title | Placebo Cohort 1 | MEDI0382 Cohort 1 | Placebo Cohort 2 | MEDI0382 Cohort 2 | TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received placebo matching with MEDI0382 subcutaneously (SC) once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. | Participants received placebo matching with MEDI0382 SC once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 14 days, followed by Dose 2 for 14 days, Dose 3 for 14 days, and Dose 4 for 7 days. | Total of all reporting groups |
| Overall Participants | 13 | 26 | 6 | 20 | 65 |
| Age (Years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [Years] |
60.2
(5.6)
|
58.7
(8.5)
|
60.3
(9.5)
|
61.9
(6.0)
|
60.1
(7.3)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
4
30.8%
|
7
26.9%
|
1
16.7%
|
10
50%
|
22
33.8%
|
| Male |
9
69.2%
|
19
73.1%
|
5
83.3%
|
10
50%
|
43
66.2%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
13
100%
|
26
100%
|
6
100%
|
20
100%
|
65
100%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||
| American Indian or Alaskan Native Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
1
3.8%
|
0
0%
|
0
0%
|
1
1.5%
|
| White |
13
100%
|
25
96.2%
|
6
100%
|
20
100%
|
64
98.5%
|
| Other |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Cohort 1: Percent Change From Baseline in Plasma Glucose Area Under the Concentration-time Curve From Time 0 to 4 Hours (AUC0-4h) by Mixed-meal Tolerance Test (MMTT) to Day 49 |
|---|---|
| Description | The MMTT test involved the consumption of a standardised liquid meal within 5 minutes and timed serial blood samples obtained for the measurement of glucose and parameters related to glucose metabolism through 240 minutes after consumption of the standardised meal (with no additional food intake during this time). The percent change in the MMTT plasma glucose AUC 0-4h from the baseline (Day -1) to Day 49 is reported. |
| Time Frame | Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised liquid meal |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamic (PD) population included all participants who received at least one dose of study drug and had at least one post-baseline MMTT PD sample or PD evaluation. |
| Arm/Group Title | Placebo Cohort 1 | MEDI0382 Cohort 1 |
|---|---|---|
| Arm/Group Description | Participants received placebo matching with MEDI0382 SC once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. |
| Measure Participants | 13 | 26 |
| Least Squares Mean (95% Confidence Interval) [Percent change] |
6.32
|
-21.52
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo Cohort 1, MEDI0382 Cohort 1 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Cohort 1: Percent Change From Baseline in Body Weight to Day 50 |
|---|---|
| Description | The percent change in body weight from baseline to Day 50 is reported. |
| Time Frame | Day 1 through Day 50 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all participants who received any study drug and were analyzed according to their randomized treatment group. |
| Arm/Group Title | Placebo Cohort 1 | MEDI0382 Cohort 1 |
|---|---|---|
| Arm/Group Description | Participants received placebo matching with MEDI0382 SC once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. |
| Measure Participants | 13 | 26 |
| Least Squares Mean (95% Confidence Interval) [Percent change] |
-0.21
|
-3.59
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo Cohort 1, MEDI0382 Cohort 1 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Cohort 1: Change From Baseline in Glycated Haemoglobin (HbA1c) to Day 49 |
|---|---|
| Description | The change from baseline in Glycated haemoglobin (HbA1c) to Day 49 is reported. |
| Time Frame | Baseline (Day -1) through Day 49 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population included all participants who received any study drug and were analyzed according to their randomized treatment group. |
| Arm/Group Title | Placebo Cohort 1 | MEDI0382 Cohort 1 |
|---|---|---|
| Arm/Group Description | Participants received placebo matching with MEDI0382 SC once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. |
| Measure Participants | 13 | 26 |
| Least Squares Mean (90% Confidence Interval) [Percentage change] |
-0.07
|
-0.67
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo Cohort 1, MEDI0382 Cohort 1 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Cohort 1: Change From Baseline in Fasting Plasma Glucose to Day 49 |
|---|---|
| Description | The changes in the fasting plasma glucose level during the study period from baseline to Day 49 is reported. |
| Time Frame | Baseline (Day -1) through Day 49 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population included all participants who received any study drug and were analyzed according to their randomized treatment group. |
| Arm/Group Title | Placebo Cohort 1 | MEDI0382 Cohort 1 |
|---|---|---|
| Arm/Group Description | Participants received placebo matching with MEDI0382 SC once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. |
| Measure Participants | 13 | 26 |
| Least Squares Mean (90% Confidence Interval) [mg/dL] |
-2.31
|
-35.37
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo Cohort 1, MEDI0382 Cohort 1 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Cohort 1: Change From Baseline in Body Weight to Day 50 |
|---|---|
| Description | The changes in the body weight during the study period from baseline to Day 50 is reported. |
| Time Frame | Day 1 through Day 50 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population included all participants who received any study drug and were analyzed according to their randomized treatment group. |
| Arm/Group Title | Placebo Cohort 1 | MEDI0382 Cohort 1 |
|---|---|---|
| Arm/Group Description | Participants received placebo matching with MEDI0382 SC once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. |
| Measure Participants | 13 | 26 |
| Least Squares Mean (90% Confidence Interval) [Kilogram] |
-0.08
|
-3.41
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo Cohort 1, MEDI0382 Cohort 1 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Cohort 1: Percentage of Participants Achieving Greater Than or Equal to 5% Body Weight Loss From Baseline to Day 50 |
|---|---|
| Description | Participants achieving greater than or equal to 5% body weight loss from baseline to Day 50 is reported. |
| Time Frame | Day 1 through Day 50 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population included all participants who received any study drug and were analyzed according to their randomized treatment group. |
| Arm/Group Title | Placebo Cohort 1 | MEDI0382 Cohort 1 |
|---|---|---|
| Arm/Group Description | Participants received placebo matching with MEDI0382 SC once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. |
| Measure Participants | 13 | 26 |
| Number [Percentage of Participants] |
7.7
59.2%
|
42.3
162.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo Cohort 1, MEDI0382 Cohort 1 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.040 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 10.76 | |
| Confidence Interval |
(2-Sided) 90% 1.61 to 72.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Cohort 1 and Cohort 2: Percent Change From Baseline in MMTT Plasma Glucose AUC 0-4h to Day 7 |
|---|---|
| Description | The MMTT test involved the consumption of a standardised liquid meal within 5 minutes and timed serial blood samples obtained for the measurement of glucose and parameters related to glucose metabolism through 240 minutes after consumption of the standardised meal (with no additional food intake during this time). The percent change in the MMTT plasma glucose AUC 0-4h from the baseline (Day -1) evaluation to Day 7 is reported. |
| Time Frame | Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised liquid meal |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PD population included all participants who received at least one dose of study drug and had at least one post-baseline MMTT PD sample or PD evaluation. The number of participants analyzed at the specified time point for this outcome measure are reported. |
| Arm/Group Title | Placebo Cohort 1 | MEDI0382 Cohort 1 | Placebo Cohort 2 | MEDI0382 Cohort 2 |
|---|---|---|---|---|
| Arm/Group Description | Participants received placebo matching with MEDI0382 subcutaneously (SC) once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. | Participants received placebo matching with MEDI0382 SC once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 14 days, followed by Dose 2 for 14 days, Dose 3 for 14 days, and Dose 4 for 7 days. |
| Measure Participants | 13 | 26 | 6 | 19 |
| Mean (Standard Deviation) [Percent change] |
-2.02
(11.70)
|
-27.17
(9.83)
|
1.77
(23.43)
|
-31.80
(7.16)
|
| Title | Cohort 1 and Cohort 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) |
|---|---|
| Description | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are the events between first doses of study drug through 7 to 14 days after the last dose of study drug (approximately 64 days). |
| Time Frame | From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| As-treated population included all participants who received any study drug and were analyzed according to the treatment they received. |
| Arm/Group Title | Placebo Cohort 1 | MEDI0382 Cohort 1 | Placebo Cohort 2 | MEDI0382 Cohort 2 |
|---|---|---|---|---|
| Arm/Group Description | Participants received placebo matching with MEDI0382 subcutaneously (SC) once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. | Participants received placebo matching with MEDI0382 SC once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 14 days, followed by Dose 2 for 14 days, Dose 3 for 14 days, and Dose 4 for 7 days. |
| Measure Participants | 13 | 26 | 6 | 20 |
| TEAEs |
6
46.2%
|
22
84.6%
|
3
50%
|
15
75%
|
| TESAEs |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Cohort 1 and Cohort 2: Number of Participants With Abnormal Vital Signs Reported as TEAEs |
|---|---|
| Description | Treatment-emergent adverse events observed in participants with clinically significant vital signs abnormalities are reported. Vital sign parameters included blood pressure, heart rate, body temperature, and respiration rate. |
| Time Frame | From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| As-treated population included all participants who received any study drug and were analyzed according to the treatment they received. |
| Arm/Group Title | Placebo Cohort 1 | MEDI0382 Cohort 1 | Placebo Cohort 2 | MEDI0382 Cohort 2 |
|---|---|---|---|---|
| Arm/Group Description | Participants received placebo matching with MEDI0382 subcutaneously (SC) once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. | Participants received placebo matching with MEDI0382 SC once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 14 days, followed by Dose 2 for 14 days, Dose 3 for 14 days, and Dose 4 for 7 days. |
| Measure Participants | 13 | 26 | 6 | 20 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Cohort 1 and Cohort 2: Number of Participants With Abnormal Electrocardiogram Reported as TEAEs |
|---|---|
| Description | Treatment-emergent adverse events observed in participants with clinically significant ECG abnormalities are reported. |
| Time Frame | From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| As-treated population included all participants who received any study drug and were analyzed according to the treatment they received. |
| Arm/Group Title | Placebo Cohort 1 | MEDI0382 Cohort 1 | Placebo Cohort 2 | MEDI0382 Cohort 2 |
|---|---|---|---|---|
| Arm/Group Description | Participants received placebo matching with MEDI0382 subcutaneously (SC) once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. | Participants received placebo matching with MEDI0382 SC once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 14 days, followed by Dose 2 for 14 days, Dose 3 for 14 days, and Dose 4 for 7 days. |
| Measure Participants | 13 | 26 | 6 | 20 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
1
5%
|
| Title | Cohort 1 and Cohort 2: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs |
|---|---|
| Description | An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator as medically significant was reported as an AE. Laboratory evaluations included haematology, serum chemistry, and urinalysis. |
| Time Frame | From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| As-treated population included all participants who received any study drug and were analyzed according to the treatment they received. |
| Arm/Group Title | Placebo Cohort 1 | MEDI0382 Cohort 1 | Placebo Cohort 2 | MEDI0382 Cohort 2 |
|---|---|---|---|---|
| Arm/Group Description | Participants received placebo matching with MEDI0382 subcutaneously (SC) once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. | Participants received placebo matching with MEDI0382 SC once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 14 days, followed by Dose 2 for 14 days, Dose 3 for 14 days, and Dose 4 for 7 days. |
| Measure Participants | 13 | 26 | 6 | 20 |
| Thrombocytopenia |
0
0%
|
0
0%
|
0
0%
|
1
5%
|
| Hypoglycaemia |
0
0%
|
1
3.8%
|
0
0%
|
1
5%
|
| Title | Cohort 1 and Cohort 2: Number of Participants With Injection Site Erythema |
|---|---|
| Description | The injection site reactions observed during study visits were reported. Injection site reactions included (but are not limited to) local erythema, pain, tenderness, induration, swelling, pruritus, ulceration, and pigmentation. |
| Time Frame | From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| As-treated population included all participants who received any study drug and were analyzed according to the treatment they received. |
| Arm/Group Title | Placebo Cohort 1 | MEDI0382 Cohort 1 | Placebo Cohort 2 | MEDI0382 Cohort 2 |
|---|---|---|---|---|
| Arm/Group Description | Participants received placebo matching with MEDI0382 subcutaneously (SC) once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. | Participants received placebo matching with MEDI0382 SC once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 14 days, followed by Dose 2 for 14 days, Dose 3 for 14 days, and Dose 4 for 7 days. |
| Measure Participants | 13 | 26 | 6 | 20 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
5
25%
|
| Title | Cohort 1: Area Under the Concentration-time Curve During the Dosing Interval (AUCt) of MEDI0382 |
|---|---|
| Description | The area under the concentration-time curve during the dosing interval of MEDI0382 is reported. |
| Time Frame | Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. |
| Arm/Group Title | MEDI0382 Cohort 1 |
|---|---|
| Arm/Group Description | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. |
| Measure Participants | 26 |
| Day 22 |
226.31
|
| Day 49 |
248.83
|
| Title | Cohort 2: Area Under the Concentration-time Curve During the Dosing Interval (AUCt) of MEDI0382 |
|---|---|
| Description | The area under the concentration-time curve during the dosing interval of MEDI0382 is reported. |
| Time Frame | Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. |
| Arm/Group Title | MEDI0382 Cohort 2 |
|---|---|
| Arm/Group Description | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 14 days, followed by Dose 2 for 14 days, Dose 3 for 14 days, and Dose 4 for 7 days. |
| Measure Participants | 20 |
| Day 1 |
38.67
|
| Day 7 |
37.51
|
| Day 14 |
46.75
|
| Title | Cohort 1: Maximum Observed Concentration (Cmax) of MEDI0382 |
|---|---|
| Description | The maximum observed concentration of MEDI0382 is reported. |
| Time Frame | Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. |
| Arm/Group Title | MEDI0382 Cohort 1 |
|---|---|
| Arm/Group Description | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. |
| Measure Participants | 26 |
| Day 22 |
13.24
|
| Day 49 |
14.8
|
| Title | Cohort 2: Maximum Observed Concentration (Cmax) of MEDI0382 |
|---|---|
| Description | The maximum observed concentration of MEDI0382 is reported. |
| Time Frame | Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. |
| Arm/Group Title | MEDI0382 Cohort 2 |
|---|---|
| Arm/Group Description | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 14 days, followed by Dose 2 for 14 days, Dose 3 for 14 days, and Dose 4 for 7 days. |
| Measure Participants | 20 |
| Day 1 |
2.00
|
| Day 7 |
2.53
|
| Day 14 |
2.65
|
| Title | Cohort 1: Time to Reach Maximum Observed Concentration (Tmax) of MEDI0382 |
|---|---|
| Description | The time to reach the maximum observed concentration of MEDI0382 is reported. |
| Time Frame | Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. |
| Arm/Group Title | MEDI0382 Cohort 1 |
|---|---|
| Arm/Group Description | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. |
| Measure Participants | 26 |
| Day 22 |
6
|
| Day 49 |
4
|
| Title | Cohort 2: Time to Reach Maximum Observed Concentration (Tmax) of MEDI0382 |
|---|---|
| Description | The time to reach the maximum observed concentration of MEDI0382 is reported. |
| Time Frame | Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. |
| Arm/Group Title | MEDI0382 Cohort 2 |
|---|---|
| Arm/Group Description | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 14 days, followed by Dose 2 for 14 days, Dose 3 for 14 days, and Dose 4 for 7 days. |
| Measure Participants | 20 |
| Day 1 |
8
|
| Day 7 |
6
|
| Day 14 |
6
|
| Title | Cohort 1: Terminal Half Life (t1/2) of MEDI0382 |
|---|---|
| Description | The t1/2 is the time measured for the concentration to decrease by one half after the dose of MEDI0382. |
| Time Frame | Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. |
| Arm/Group Title | MEDI0382 Cohort 1 |
|---|---|
| Arm/Group Description | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. |
| Measure Participants | 6 |
| Day 22 |
9.67
|
| Day 49 |
8.4
|
| Title | Cohort 2: Terminal Half Life (t1/2) of MEDI0382 |
|---|---|
| Description | The t1/2 is the time measured for the concentration to decrease by one half after the dose of MEDI0382. |
| Time Frame | Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. |
| Arm/Group Title | MEDI0382 Cohort 2 |
|---|---|
| Arm/Group Description | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 14 days, followed by Dose 2 for 14 days, Dose 3 for 14 days, and Dose 4 for 7 days. |
| Measure Participants | 5 |
| Day 1 |
9.7
|
| Day 7 |
8.8
|
| Day 14 |
9.4
|
| Title | Cohort 1: Accumulation Ratio (Racc) of MEDI0382 |
|---|---|
| Description | The Racc was calculated using the AUC method which account for the overall exposure measured using the specified time points on Day 22 and Day 49. Racc was calculated using the formula, Racc of Day 49 = AUCt of Day 49/AUCt of Day 22. |
| Time Frame | Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. |
| Arm/Group Title | MEDI0382 Cohort 1 |
|---|---|
| Arm/Group Description | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. |
| Measure Participants | 21 |
| Geometric Mean (Full Range) [Ratio] |
1.46
|
| Title | Cohort 2: Accumulation Ratio of MEDI0382 |
|---|---|
| Description | The Racc was calculated using the AUC method which account for the overall exposure measured using the specified time points on Day 1, Day 7 and Day 14. Racc was calculated using the formulas: Racc of Day 7 = AUCt of Day 7/AUCt of Day 1; Racc of Day 14 = AUCt of Day 14/AUCt of Day 1. |
| Time Frame | Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. |
| Arm/Group Title | MEDI0382 Cohort 2 |
|---|---|
| Arm/Group Description | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 14 days, followed by Dose 2 for 14 days, Dose 3 for 14 days, and Dose 4 for 7 days. |
| Measure Participants | 20 |
| Day 7 |
1.36
|
| Day 14 |
1.46
|
| Title | Cohort 1: Trough Plasma Concentration (Ctrough) of MEDI0382 |
|---|---|
| Description | Trough plasma concentration is the measured concentration from the plasma concentration-time data at the end of a dosing interval at steady state. |
| Time Frame | Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. |
| Arm/Group Title | MEDI0382 Cohort 1 |
|---|---|
| Arm/Group Description | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. |
| Measure Participants | 26 |
| Day 22 |
3.566
|
| Day 49 |
5.762
|
| Title | Cohort 2: Trough Plasma Concentration (Ctrough) of MEDI0382 |
|---|---|
| Description | Trough plasma concentration is the measured concentration from the plasma concentration time data at the end of a dosing interval at steady state. |
| Time Frame | Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. |
| Arm/Group Title | MEDI0382 Cohort 2 |
|---|---|
| Arm/Group Description | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 14 days, followed by Dose 2 for 14 days, Dose 3 for 14 days, and Dose 4 for 7 days. |
| Measure Participants | 20 |
| Day 7 |
1.147
|
| Day 14 |
1.147
|
| Title | Cohort 1 and Cohort 2: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0382 |
|---|---|
| Description | Participants with positive serum antibodies to MEDI0382 are reported. |
| Time Frame | Baseline (Day 1), Day 29, Day 50, and Follow-up Visit 2 (28 days after the last dose [approximately 64 days]) |
Outcome Measure Data
| Analysis Population Description |
|---|
| As-treated population included all participants who received any study drug and were analyzed according to the treatment they received. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. |
| Arm/Group Title | Placebo Cohort 1 | MEDI0382 Cohort 1 | Placebo Cohort 2 | MEDI0382 Cohort 2 |
|---|---|---|---|---|
| Arm/Group Description | Participants received placebo matching with MEDI0382 subcutaneously (SC) once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. | Participants received placebo matching with MEDI0382 SC once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 14 days, followed by Dose 2 for 14 days, Dose 3 for 14 days, and Dose 4 for 7 days. |
| Measure Participants | 13 | 26 | 6 | 20 |
| Baseline (ADA positive) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Day 29 (ADA positive) |
0
0%
|
4
15.4%
|
0
0%
|
1
5%
|
| Day 50 (ADA positive) |
0
0%
|
7
26.9%
|
0
0%
|
2
10%
|
| Follow-up Visit 2 (ADA positive) |
1
7.7%
|
6
23.1%
|
0
0%
|
6
30%
|
Adverse Events
| Time Frame | From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days) | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Placebo Cohort 1 | MEDI0382 Cohort 1 | Placebo Cohort 2 | MEDI0382 Cohort 2 | ||||
| Arm/Group Description | Participants received placebo matching with MEDI0382 subcutaneously (SC) once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. | Participants received placebo matching with MEDI0382 SC once daily for 49 days. | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 14 days, followed by Dose 2 for 14 days, Dose 3 for 14 days, and Dose 4 for 7 days. | ||||
All Cause Mortality |
||||||||
| Placebo Cohort 1 | MEDI0382 Cohort 1 | Placebo Cohort 2 | MEDI0382 Cohort 2 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/13 (0%) | 0/26 (0%) | 0/6 (0%) | 0/20 (0%) | ||||
Serious Adverse Events |
||||||||
| Placebo Cohort 1 | MEDI0382 Cohort 1 | Placebo Cohort 2 | MEDI0382 Cohort 2 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/13 (0%) | 0/26 (0%) | 0/6 (0%) | 0/20 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Placebo Cohort 1 | MEDI0382 Cohort 1 | Placebo Cohort 2 | MEDI0382 Cohort 2 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/13 (46.2%) | 22/26 (84.6%) | 3/6 (50%) | 15/20 (75%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Thrombocytopenia | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/6 (0%) | 0 | 1/20 (5%) | 1 |
| Cardiac disorders | ||||||||
| Tachycardia | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/6 (0%) | 0 | 1/20 (5%) | 1 |
| Eye disorders | ||||||||
| Visual impairment | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/6 (0%) | 0 | 1/20 (5%) | 1 |
| Gastrointestinal disorders | ||||||||
| Abdominal discomfort | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/6 (0%) | 0 | 1/20 (5%) | 1 |
| Abdominal pain | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Abdominal wall haematoma | 1/13 (7.7%) | 1 | 0/26 (0%) | 0 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Constipation | 0/13 (0%) | 0 | 4/26 (15.4%) | 4 | 0/6 (0%) | 0 | 1/20 (5%) | 1 |
| Diarrhoea | 1/13 (7.7%) | 1 | 3/26 (11.5%) | 4 | 0/6 (0%) | 0 | 1/20 (5%) | 1 |
| Dyspepsia | 0/13 (0%) | 0 | 4/26 (15.4%) | 8 | 0/6 (0%) | 0 | 2/20 (10%) | 3 |
| Eructation | 0/13 (0%) | 0 | 3/26 (11.5%) | 4 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Flatulence | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Nausea | 0/13 (0%) | 0 | 5/26 (19.2%) | 8 | 0/6 (0%) | 0 | 7/20 (35%) | 11 |
| Parotid gland enlargement | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/6 (0%) | 0 | 1/20 (5%) | 1 |
| Regurgitation | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/6 (0%) | 0 | 1/20 (5%) | 1 |
| Tongue discomfort | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/6 (0%) | 0 | 1/20 (5%) | 2 |
| Toothache | 0/13 (0%) | 0 | 2/26 (7.7%) | 3 | 0/6 (0%) | 0 | 1/20 (5%) | 1 |
| Vomiting | 0/13 (0%) | 0 | 3/26 (11.5%) | 6 | 0/6 (0%) | 0 | 4/20 (20%) | 11 |
| General disorders | ||||||||
| Face oedema | 0/13 (0%) | 0 | 1/26 (3.8%) | 2 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Fatigue | 1/13 (7.7%) | 1 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Induration | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/6 (0%) | 0 | 1/20 (5%) | 1 |
| Injection site erythema | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/6 (0%) | 0 | 5/20 (25%) | 7 |
| Injection site haematoma | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/6 (0%) | 0 | 1/20 (5%) | 1 |
| Injection site reaction | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/6 (0%) | 0 | 1/20 (5%) | 2 |
| Malaise | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Medical device site pain | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Medical device site swelling | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Oedema peripheral | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Pyrexia | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Vessel puncture site haematoma | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Infections and infestations | ||||||||
| Conjunctivitis | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/6 (0%) | 0 | 1/20 (5%) | 1 |
| Nasal herpes | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Rhinitis | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Urinary tract infection | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/6 (0%) | 0 | 2/20 (10%) | 2 |
| Viral upper respiratory tract infection | 3/13 (23.1%) | 4 | 3/26 (11.5%) | 4 | 0/6 (0%) | 0 | 3/20 (15%) | 4 |
| Injury, poisoning and procedural complications | ||||||||
| Contusion | 1/13 (7.7%) | 1 | 0/26 (0%) | 0 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Procedural nausea | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 2/13 (15.4%) | 2 | 13/26 (50%) | 17 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Gout | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Hypoglycaemia | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 1/20 (5%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 1/13 (7.7%) | 1 | 0/26 (0%) | 0 | 1/6 (16.7%) | 2 | 0/20 (0%) | 0 |
| Osteoarthritis | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Pain in extremity | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Nervous system disorders | ||||||||
| Dizziness | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 1/20 (5%) | 1 |
| Headache | 0/13 (0%) | 0 | 2/26 (7.7%) | 2 | 2/6 (33.3%) | 2 | 4/20 (20%) | 6 |
| Tremor | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/6 (0%) | 0 | 1/20 (5%) | 5 |
| Psychiatric disorders | ||||||||
| Loss of libido | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Nocturia | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||
| Vaginal haemorrhage | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 1/6 (16.7%) | 1 | 0/20 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 1/6 (16.7%) | 1 | 0/20 (0%) | 0 |
| Epistaxis | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Nasal obstruction | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 1/6 (16.7%) | 1 | 0/20 (0%) | 0 |
| Oropharyngeal pain | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 1/20 (5%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||
| Dermatitis contact | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Erythema | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/6 (0%) | 0 | 1/20 (5%) | 1 |
| Hyperhidrosis | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/6 (0%) | 0 | 1/20 (5%) | 1 |
| Rash | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
| Skin reaction | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/6 (0%) | 0 | 0/20 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
Results Point of Contact
| Name/Title | Victoria Parker |
|---|---|
| Organization | MedImmune Limited |
| Phone | +44 747 1357152 |
| information.center@astrazeneca.com |
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