A Study to Look at the Effect MEDI0382 Has on Blood Sugar in People With Type 2 Diabetes and Kidney Problems and Also to Check That MEDI0382 is Well Tolerated

Renal Insufficiency Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03550378
• Other study ID #: D5670C00013
• Secondary ID: 2018-000019-26
• Status: Completed
• Phase: Phase 2
• Start date: June 29, 2018
• Est. completion date: February 4, 2019

Study information

• Verified date: March 2020
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A study to look at the effect MEDI0382 has on blood sugar in people with type 2 diabetes and kidney problems and also to check that MEDI0382 is well tolerated.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: February 4, 2019
• Est. primary completion date: February 4, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 84 Years

Eligibility

Inclusion Criteria:

1. Age = 18 and < 85 years at screening.

2. Signed and dated written informed consent (with the exception of consent for genetic and nongenetic research) prior to performing any protocol-related procedures, including screening evaluations.

3. Diagnosed with type 2 diabetes mellitus (T2DM) with glucose control managed with any insulin and/or oral therapy combination where no significant dose changes of oral therapy of more than 50% have occurred in the 3 months prior to screening

4. Body mass index (BMI) between 25 and 45 kg/m^2 (inclusive) at screening

5. Haemoglobin A1c (HbA1c) range of 6.5 % to 10.5% (inclusive) at screening

6. Renal impairment with estimated glomerular filtration rate (eGFR) = 30 and < 60 mL/min/1.73 m^2 at screening. Approximately 16 participants (40%) are required to have a screening eGFR =30 and < 45 mL/min/1.73 m^2 and at least 16 participants (40%) are required to have screening eGFR =45 and < 60 mL/min/1.73 m^2.

7. Females of childbearing potential must have a negative pregnancy test at screening and randomisation, and must not be lactating. Women of childbearing potential who are sexually active with a non-sterilized male partner must be using at least one highly effective method of contraception from screening and up to 4 weeks after the last dose study drug.

Exclusion Criteria:

1. History or presence of significant medical or psychological conditions, including substance dependence/abuse, or significant abnormalities in laboratory parameters or vital signs including electrocardiogram (ECG), which in the opinion of the investigator, would compromise the participant's safety or successful participation in the study. As an example, severe anaemia (haemoglobin < 7.0 g/dL) could be exclusionary due to blood sampling required by the protocol, at the discretion of investigator.

2. Concurrent participation in another interventional study of any kind and repeat randomisation in this study is prohibited.

3. Any participant who has received another study drug as part of a clinical study or a glucagon-like peptide-1 (GLP-1) analogue-containing preparation within the last 30 days or 5 half-lives of the drug (if known; whichever is longer) at the time of Visit 2.

4. Any participant who has received any of the following medications within the specified timeframe prior to the start of the study (Visit 2)

• Herbal preparations within 1 week prior to the start of dosing (Visit 4) or drugs licensed for control of body weight or appetite (eg, orlistat, bupropion-naltrexone, phentermine-topiramate, phentermine, lorcaserin) within 30 days (or 5 half-lives of the drug) prior to the start of dosing (Visit 4)

• Aspirin (acetylsalicylic acid) at a dose greater than 150 mg once daily and within the last 3 days prior to the start of the run-in period (Visit 2)

• Paracetamol (acetaminophen) or paracetamol-containing preparations at a total daily dose of greater than 3000 mg and within the last 3 days prior to the start of the run-in period (Visit 2)

• Ascorbic acid (vitamin C) supplements at a total daily dose of greater than 1000 mg and within the last 3 days prior to the start of the run-in period (Visit 2)

• Opiates, domperidone, metoclopramide, or other drugs known to alter gastric emptying and within 2 weeks prior to the start of dosing (Visit 4)

5. Severe allergy/hypersensitivity to any of the proposed study treatments or excipients

6. Symptoms of acutely decompensated blood glucose control (eg, thirst, polyuria, weight loss), a history of type 1 diabetes mellitus or diabetic ketoacidosis

7. Participants who have undergone a renal transplant

8. Participants with suspicion of acute or subacute renal function deterioration (eg, participants with large fluctuations of creatinine values documented within the 6 months prior to screening)

9. Significant inflammatory bowel disease, gastroparesis, or other severe disease or surgery affecting the upper gastrointestinal (GI) tract including weight-reducing surgery and procedures) which may affect gastric emptying or could affect the interpretation of safety and tolerability data

10. History of acute or chronic pancreatitis

11. Significant hepatic disease (except for non-alcoholic steatohepatitis or nonalcoholic fatty liver disease without portal hypertension or cirrhosis) and/or participants with any of the following results:

• Aspartate transaminase (AST) = 3 × upper limit of normal (ULN)

• Alanine transaminase (ALT) = 3 × ULN

• Total bilirubin = 2 × ULN

12. Poorly controlled hypertension defined as:

• Systolic blood pressure (BP) > 180 mm Hg

• Diastolic BP = 100 mm Hg Participants who fail BP screening criteria may be considered for 24-hour ambulatory blood pressure monitoring (ABPM) at the discretion of the investigator. Participants who maintain a mean 24-hour systolic BP = 180 or diastolic BP < 100 mm Hg with a preserved nocturnal dip of > 15% will be considered eligible

13. Unstable angina pectoris, myocardial infarction, transient ischemic attack or stroke within 3 months prior to screening, or participants 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

14. Severe congestive heart failure (New York Heart Association Class III or IV)

15. Basal calcitonin level > 50 ng/L at screening or history/family history of medullary thyroid carcinoma or multiple endocrine neoplasia

16. History of neoplastic disease within 5 years prior to screening, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer

17. Any positive results for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody, and human immunodeficiency virus (HIV) antibody

18. Nephrotic range proteinuria defined as spot urine albumin creatinine ratio (ACR) > 250 mg/mmol at screening

19. 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 Day -5. Participants 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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Renal Insufficiency
• Type II Diabetes Mellitus

Intervention

Drug:
• MEDI0382
Participants will receive subcutaneous 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.
• Placebo
Participants will receive SC placebo matched to MEDI0382 once daily for 32 days.

Locations

Country	Name	City	State
Germany	Research Site	Berlin
Germany	Research Site	Magdeburg
Germany	Research Site	München
Germany	Research Site	Munster
United Kingdom	Research Site	Dundee
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	Edinburgh

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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 standardized meal (with no additional food intake during this time).	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
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	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.	Day 1 through Day 60
Secondary	Number of Participants With Abnormal Vital Signs Reported as TEAEs	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).	Day 1 through Day 60
Secondary	Change From Baseline in Postural Blood Pressure	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 analyzed. 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.	Baseline (Day 1) through Day 32
Secondary	Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs	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.	Day 1 through Day 60
Secondary	Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs	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.	Day 1 through Day 60
Secondary	Number of Participants With Treatment-emergent Adverse Events of Special Interest (TEAESIs)	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.	Day 1 through Day 60
Secondary	Change From Baseline in Mean 24-hrs Pulse Rate to the End of Each Dosing Level	Change from baseline in mean 24-hrs pulse rate to the end of each dosing levels: Day 5 for 50 µg; Day 12 for 100 µg, Day 19 for 200 µg, and Day 32 for 300 µg.	Day -5 (Baseline) and on Days 5, 12, 19, and 32
Secondary	Change From Baseline in Mean 24-hrs Systolic and Diastolic Blood Pressure to the End of Each Dosing Level	Change from baseline in mean 24-hrs systolic and diastolic blood pressure to the end of each dosing levels: Day 5 for 50 µg, Day 12 for 100 µg, Day 19 for 200 µg, and Day 32 for 300 µg.	Day -5 (Baseline) and on Days 5, 12, 19, and 32
Secondary	Change From Baseline in Haemoglobin A1c (HbA1c) to Day 32	Change from baseline in haemoglobin A1c (HbA1c) is reported.	Day 1 (Baseline) and Day 32
Secondary	Change From Baseline in Fasting Glucose to Day 32	Change from baseline in fasting glucose is reported.	Day 1 (Baseline) and Day 32
Secondary	Change From Baseline in Percentage of Time Spent Within a Target Glucose Range Over a 7-day Period to the Final Week of Treatment	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).	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)
Secondary	Percent Change Frome Baseline in Body Weight to Day 33	Percent change from baseline in body weight is reported.	Day 1 (Baseline) and Day 33
Secondary	Change From Baseline in Absolute Body Weight to Day 33	Change from baseline in absolute body weight is reported.	Day 1 (Baseline) and Day 33
Secondary	Area Under the Plasma Concentration Time Curve Over a Dosing Duration (AUCt) of MEDI0382 at 300 µg	Area under the plasma concentration time curve over a dosing duration (AUCt) of MEDI0382 at 300 µg is reported.	Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose on Day 32
Secondary	Maximum Observed Serum Concentration (Cmax) of MEDI0382 at 300 µg	Maximum observed serum concentration (Cmax) of MEDI0382 at 300 µg is reported.	Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose on Day 32
Secondary	Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382 at 300 µg	Time to observed maximum serum concentration (Tmax) of MEDI0382 at 300 µg is reported.	Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose on Day 32
Secondary	Trough Plasma Concentration (Ctrough) of MEDI0382	Trough concentration is the lowest concentration reached by a drug before the next dose is administered. Trough plasma concentration of MEDI0382 is reported.	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)
Secondary	Number of Participants With Positive Anti-drug Antibodies (ADA) Titre to MEDI0382	Number of participants with positive Anti-drug antibodies (ADA) Titre to MEDI0382 is reported.	Pre-dose on Days 1, 12, and 32 and on Day 60

External Links

•   D5670C00013 - SAP_Redacted
•   D5670C00013 CSP redacted