Clinical Trial Results:
A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MEDI0382 in Subjects with Type 2 Diabetes Mellitus and Renal Impairment
Summary
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EudraCT number |
2018-000019-26 |
Trial protocol |
GB |
Global end of trial date |
04 Feb 2019
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Results information
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Results version number |
v3(current) |
This version publication date |
26 Apr 2020
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First version publication date |
28 Feb 2020
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Other versions |
v1 , v2 |
Version creation reason |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
D5670C00013
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03550378 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
MedImmune, a wholly owned subsidiary of Astrazeneca
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Sponsor organisation address |
Milstein Building, Granta Park, Cambridge, United Kingdom, CB21 6GH
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Public contact |
Lars Hansen, MedImmune, a wholly owned subsidiary of Astrazeneca, +1 301-398-4563, information.center@astrazeneca.com
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Scientific contact |
Lars Hansen, MedImmune, a wholly owned subsidiary of Astrazeneca, +1 301-398-4563, information.center@astrazeneca.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
09 Aug 2019
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
04 Feb 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of the study was to asses the safety and efficacy of MEDI0382 titrated up to a dose level of 300 µg on glucose control versus Placebo after 32 days of treatment in participants with type 2 diabetes mellitus (T2DM) and renal impairment.
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Protection of trial subjects |
The conduct of this clinical study met all local and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and are consistent with International Conference on Harmonization guideline: Good Clinical Practice, and applicable regulatory requirements. Participants signed an informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
29 Jun 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 9
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Country: Number of subjects enrolled |
Germany: 32
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Worldwide total number of subjects |
41
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EEA total number of subjects |
41
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
5
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From 65 to 84 years |
36
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted in the United Kingdom and Germany between 29Jun2018 and 04Feb2019. | |||||||||||||||
Pre-assignment
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Screening details |
A total of 41 participants were randomized to the study. | |||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | |||||||||||||||
Arm description |
Participants received subcutaneous dose (SC) dose of placebo matched to MEDI0382 once daily for 32 days. | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subcutaneous (SC) dose of placebo matched to MEDI0382 once daily for 32 days.
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Arm title
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MEDI0382 | |||||||||||||||
Arm description |
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
MEDI0382
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
The SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Participants received subcutaneous dose (SC) dose of placebo matched to MEDI0382 once daily for 32 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MEDI0382
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Reporting group description |
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Participants received subcutaneous dose (SC) dose of placebo matched to MEDI0382 once daily for 32 days. | ||
Reporting group title |
MEDI0382
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Reporting group description |
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days. |
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End point title |
Percent Change From Baseline in Plasma Glucose Area Under the Concentration Time-curve From Time 0 to 4 hours (AUC0-4 hrs) as Measured by Mixed-meal Tolerance Test (MMTT) to Day 32 | ||||||||||||
End point description |
The MMTT involved the consumption of a standardised liquid meal (a nutritional supplement containing the components of fat, carbohydrate, and protein, which make up a standard MMTT) within 15 minutes, and timed serial blood samples obtained for 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). Intent-to-treat (ITT) population was analysed for this endpoint, which included all participants who received any dose of study drug and analysed according to their randomised treatment group.
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End point type |
Primary
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End point timeframe |
Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised meal on Day -5 (Baseline) and Day 32
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Statistical analysis title |
Comparison in percent change of glucose AUC | ||||||||||||
Comparison groups |
Placebo v MEDI0382
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Number of subjects included in analysis |
38
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
< 0.001 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||
Point estimate |
-30.384
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Confidence interval |
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level |
90% | ||||||||||||
sides |
2-sided
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lower limit |
-41.27 | ||||||||||||
upper limit |
-19.498 |
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End point title |
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | |||||||||||||||
End point description |
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (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. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. As-treated population was analysed for this endpoint, which included all participants who received any dose of study drug and analysed according to the treatment they actually received.
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End point type |
Secondary
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End point timeframe |
Day 1 through Day 60
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No statistical analyses for this end point |
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End point title |
Number of Participants With Abnormal Vital Signs Reported as TEAEs | |||||||||
End point description |
Number of participants with abnormal vital signs reported as TEAEs is reported. Vital sign measurements were obtained after the participant had rested in the supine position for at least 10 minutes at the recording time. Abnormal vital signs is defined as any abnormal finding in the vital sign parameters (blood pressure, pulse rate, body temperature, and respiratory rate). As-treated population was analysed for this endpoint, which included all participants who received any dose of study drug and analysed according to the treatment they actually received.
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End point type |
Secondary
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End point timeframe |
Day 1 through Day 60
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Postural Blood Pressure | ||||||||||||||||||
End point description |
The change difference is the change from Day 1 to Day 32 in the difference between systolic blood pressure (SBP) or diastolic blood pressure (DBP) values in standing and supine positions. For this outcome measure, participants with difference (standing-supine) in DBP or SBP on Day 1 and Day 32 were analysed. For few participants either DBP or SBP was recorded eg, standing DBP was not recorded on Day 1 for 2 participants in Placebo arm and 1 participant in MEDI0382 arm; standing SBP was not recorded on Day 32 for a participant in the Placebo arm. As-treated population was analysed for this endpoint, which included all participants who received any dose of study drug and analysed according to the treatment they actually received. Participants with difference (standing-supine) in DBP or SBP on Day 1 and the participants with difference (standing-supine) in DBP or SBP on Day 32 were analysed.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) through Day 32
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No statistical analyses for this end point |
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End point title |
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs | ||||||||||||||||||
End point description |
Number of participants with abnormal ECGs reported as TEAEs is reported. Abnormal ECGs is defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, axis, ST-T morphology, and QT intervals from the primary lead of the digital 12-lead ECG. As-treated population was analysed for this endpoint, which included all participants who received any dose of study drug and analysed according to the treatment they actually received.
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End point type |
Secondary
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End point timeframe |
Day 1 through Day 60
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No statistical analyses for this end point |
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End point title |
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | |||||||||||||||||||||
End point description |
Number of participants with abnormal clinical laboratory parameters reported as TEAEs is reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, and urine. As-treated population was analysed for this endpoint, which included all participants who received any dose of study drug and analysed according to the treatment they actually received.
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End point type |
Secondary
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End point timeframe |
Day 1 through Day 60
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No statistical analyses for this end point |
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End point title |
Number of Participants With Treatment-emergent Adverse Events of Special Interest (TEAESIs) | |||||||||
End point description |
An adverse event of special interest (AESI) was one of scientific and medical interest specific to understanding of the study drug and may require close monitoring and rapid communication by the investigator to the sponsor. As-treated population was analysed for this endpoint, which included all participants who received any dose of study drug and analysed according to the treatment they actually received.
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End point type |
Secondary
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End point timeframe |
Day 1 through Day 60
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Mean 24-hrs Pulse Rate to the End of Each Dosing Level | ||||||||||||||||||||||||
End point description |
Change from baseline in mean 24-hrs pulse rate to the end of each dosing levels. End of dosing: Day 5 for 50 μg; Day 12 for 100 μg, Day 19 for 200 μg, and Day 32 for 300 μg. As-treated population was analysed for this endpoint, which included all participants who received any dose of study drug and analysed according to the treatment they actually received. Here, "n" signifies only the participants with available data were analysed for the specified time points.
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End point type |
Secondary
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End point timeframe |
Day -5 (Baseline) and on Days 5, 12, 19, and 32
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Mean 24-hrs Systolic and Diastolic Blood Pressure to the end of Each Dosing Level | ||||||||||||||||||||||||||||||||||||
End point description |
Change from baseline in mean 24-hrs systolic and diastolic blood pressure to the end of each dosing levels. End of dosing: Day 5 for 50 μg; Day 12 for 100 μg, Day 19 for 200 μg, and Day 32 for 300 μg. As-treated population was analysed for this endpoint, which included all participants who received any dose of study drug and analysed according to the treatment they actually received. Here, "n" signifies only the participants with available data were analyzed for the specified time points.
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End point type |
Secondary
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End point timeframe |
Day -5 (Baseline) and on Days 5, 12, 19, and 32
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Haemoglobin A1c (HbA1c) to Day 32 | ||||||||||||
End point description |
Change from baseline in haemoglobin A1c (HbA1c) is reported. An ITT population was analysed for this endpoint, which included all participants who received any dose of study drug and analysed according to their randomised treatment group.
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End point type |
Secondary
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End point timeframe |
Day 1 (Baseline) and Day 32
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Fasting Glucose to Day 32 | ||||||||||||
End point description |
Change from baseline in fasting glucose is reported. An ITT population was analysed for this endpoint, which included all participants who received any dose of study drug and analysed according to their randomised treatment group.
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End point type |
Secondary
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End point timeframe |
Day 1 (Baseline) and Day 32
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Percentage of Time Spent Within a Target Glucose Range Over a 7-day Period to the Final Week of Treatment | ||||||||||||||||||||||||
End point description |
Change from baseline in percentage of time spent within a target glucose range over a 7-day period to the final week of treatment is reported. Target glucose range was considered as 70 mg/dL (3.9 mmol/L) to 180 mg/dL (10 mmol/L). An ITT population was analysed for this endpoint, which included all participants who received any dose of study drug and analysed according to their randomised treatment group. Here, "n" signifies only the participants with available data were analyzed for the specified time points.
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End point type |
Secondary
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End point timeframe |
Baseline (Days -8 to -2), Days 5 to 11, Days 12 to 18, Days 19 to 25, and Days 26 to 32 (final week of treatment)
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No statistical analyses for this end point |
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End point title |
Percent Change Frome Baseline in Body Weight to Day 33 | ||||||||||||
End point description |
Percent change from baseline in body weight is reported. An ITT population was analysed for this endpoint, which included all participants who received any dose of study drug and analysed according to their randomised treatment group.
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End point type |
Secondary
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End point timeframe |
Day 1 (Baseline) and Day 33
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Absolute Body Weight to Day 33 | ||||||||||||
End point description |
Change from baseline in absolute body weight is reported. An ITT population was analysed for this endpoint, which included all participants who received any dose of study drug and analysed according to their randomised treatment group.
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End point type |
Secondary
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End point timeframe |
Day 1 (Baseline) and Day 33
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No statistical analyses for this end point |
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End point title |
Area Under the Plasma Concentration Time Curve Over a Dosing Duration (AUCτ) of MEDI0382 at 300 μg [1] | ||||||||
End point description |
Area under the plasma concentration time curve over a dosing duration (AUCτ) of MEDI0382 at 300 μg is reported. Pharmacokinetic (PK) population was analysed for this endpoint, which included all participants who received at least 1 dose of study drug and had at least one PK sample collected with a value above the lower limit of quantitation.
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End point type |
Secondary
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End point timeframe |
Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose on Day 32
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Notes [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only those baseline period arms for which analysis was planned were reported in the end point |
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No statistical analyses for this end point |
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End point title |
Maximum Observed Serum Concentration (Cmax) of MEDI0382 at 300 μg [2] | ||||||||
End point description |
Maximum observed serum concentration (Cmax) of MEDI0382 at 300 μg is reported. The PK population was analysed for this endpoint, which included all participants who received at least 1 dose of study drug and had at least one PK sample collected with a value above the lower limit of quantitation.
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End point type |
Secondary
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End point timeframe |
Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose on Day 32
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Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only those baseline period arms for which analysis was planned were reported in the end point |
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No statistical analyses for this end point |
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End point title |
Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382 at 300 μg [3] | ||||||||
End point description |
Time to observed maximum serum concentration (Tmax) of MEDI0382 at 300 μg is reported. The PK population was analysed for this endpoint, which included all participants who received at least 1 dose of study drug and had at least one PK sample collected with a value above the lower limit of quantitation.
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End point type |
Secondary
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End point timeframe |
Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose on Day 32
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Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only those baseline period arms for which analysis was planned were reported in the end point |
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No statistical analyses for this end point |
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End point title |
Trough Plasma Concentration (Ctrough) of MEDI0382 [4] | ||||||||||||||||||||
End point description |
Trough concentration is the lowest concentration reached by a drug before the next dose is administered. Trough plasma concentration (Ctrough) of MEDI0382 reported. The PK population was analysed for this endpoint, which included all participants who received at least 1 dose of study drug and had at least one PK sample collected with a value above the lower limit of quantitation. Here, "n" signifies only the participants with available data were analysed for the specified time points. Here, the arbitrary number "9999" signifies that the data is not reported as no participants were evaluable for the specified time point.
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End point type |
Secondary
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End point timeframe |
Days 1, 5, 12, and 19: Predose; and Day 32: Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose (Day 33)
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Notes [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only those baseline period arms for which analysis was planned were reported in the end point |
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No statistical analyses for this end point |
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End point title |
Number of Participants With Positive Anti-drug antibodies (ADA) Titre to MEDI0382 | ||||||||||||||||||||||||
End point description |
Number of participants with positive Anti-drug antibodies (ADA) Titre to MEDI0382 is reported. As-treated population was analysed for this endpoint, which included all participants who received any dose of study drug and analysed according to the treatment they actually received.
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End point type |
Secondary
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End point timeframe |
Pre-dose on Days 1, 12, and 32 and on Day 60
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Day 1 through Day 60
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.0
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Reporting groups
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Reporting group title |
MEDI0382
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Reporting group description |
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Participants received subcutaneous dose (SC) dose of placebo matched to MEDI0382 once daily for 32 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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28 Feb 2018 |
Addition of weight to schedule of assessments on Day 32. Text modified to state electrocardiogram (ECG) is from lead II on V2. Added a prohibited concomitant medication. Added a prohibited concomitant medication. |
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06 Apr 2018 |
Changes to discontinuation of study drug criteria. Updated to add a 2-hour post-dose ECG on Days 1 and 32. Added amylase and lipase sampling at Days 5, 12 and 19. Updated that all deaths (including those that are clearly the result of disease progression) reported as a serious adverse event (SAE). |
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11 Oct 2018 |
Planned interim analysis was removed. |
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12 Nov 2018 |
“At least” was changed to “Approximately” in regard to eligible participants in the estimated glomerular filtration rate 30 to 45 mL/min/1.73 m^2 category. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |