Study of Exenatide Once-Weekly Suspension in Chinese Patients With Type 2 Diabetes Mellitus
Primary Purpose
Type 2 Diabetes
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Exenatide Once-Weekly Suspension
Sponsored by
About this trial
This is an interventional other trial for Type 2 Diabetes focused on measuring Pharmacokinetics, Safety, Tolerability, exenatide once weekly, Chinese
Eligibility Criteria
Inclusion Criteria:
- Provision of informed consent prior to any study-specific procedures.
- Male or female patients with T2DM treated with diet modification and exercise alone or in combination with a stable (in PI's opinion) regimen of metformin only for at least two months prior to screening. The T2DM diagnosis will be confirmed clinically by the PI, and should be consistent with the World Health Organization criteria for diagnosis and classification of diabetes
- Between 20 to 75 years of age inclusive at Visit 1 (Screening)
The following criterion applies to females of child-bearing potential (not surgically sterilized and between menarche and 1-year postmenopause) only:
- Test negative for pregnancy at the time of screening.
- Intend not to become pregnant during the study.
- Are sexually inactive or have practiced a reliable method of birth control (for example, use of oral contraceptives or levonorgestrel, diaphragms with contraceptive jelly, cervical caps with contraceptive jelly, condoms with contraceptive foam, intrauterine devices, partner with vasectomy) for at least 6 weeks prior to screening.
- Agree to continue to use a reliable method of birth control (as determined by the PI) during the study and until 90 days after last dose.
- Have a body weight of ≥45 kg and a body mass index (BMI) of 18.5 to 35 kg/m2 inclusive at Visit 1 (Screening).
- Have clinical laboratory test results within the normal reference range for the population or study site, or with abnormalities deemed clinically insignificant by the PI. Abnormalities of plasma glucose (fasting ≤12.0 mmol/L and anytime≤15.0mmol/L), HbA1c (<10.5%), plasma lipids (TG<5.7 mmol/L), and urinary protein (with a range of trace < 2+ on dipstick) are acceptable.
- Venous access sufficient to allow blood sampling as per the protocol.
- Are reliable and willing to be available for the duration of the study and are willing to follow study procedures.
Exclusion Criteria:
- Involvement in the planning and/or conduct of the study (applies to bothAstraZeneca staff and/or staff at the study site, and direct family members).
- Previous enrollment in the present study or have previously completed or withdrawn from any other study investigating exenatide.
- Within 30 days of the initial dose of IP, have received treatment with a drug that has not received regulatory approval for any indication.
- Known allergy or hypersensitivity to exenatide or any of the excipients contained in these agents (exenatide: sodium acetate buffer, mannitol, metacresol, MCT vehicle).
- Previous treatment with exenatide or related GLP-1 receptor agonist compounds.
- History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, haematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data.
- Systolic blood pressure (SBP) persistently (on ≥2 separate occasions) >160 mmHg on stable regimen of antihypertensive medication or >180 mmHg regardless of antihypertensive treatment.
- History of, or currently have angina, revascularization, myocardial infarction, or heart failure.
- Clinically significant peripheral vascular disease.
Evidence of poorly controlled T2DM or evidence of significant diabetes-related complications such as:
- Plasma glucose >12 mmol/L (fasting) or >15 mmol/L (anytime) at Visit 1 (Screening)
- HbA1c >10.5%
- History of hypoglycemic or hyperglycemic coma within 1 year prior to Visit 1 (Screening)
- History of active diabetic proliferative retinopathy or macular oedema
- Known significant autonomic neuropathy as evidenced by urinary retention, orthostatic hypotension, diabetic diarrhea, or gastroparesis
- Two or more episodes of major hypoglycemia within 6 months prior to Visit 1 (Screening). See Section 5.2.8.1 for hypoglycemia classification.
- Impaired renal function (serum creatinine >125 μ/mol/L in women, >132 μ/mol/L in men).
- Liver disease, acute or chronic hepatitis, alanine aminotransferase (ALT/SGPT), or aspartate aminotransferase (AST) ≥3x upper limit of normal (ULN) of the reference range and total bilirubin level (TBL) ≥2xULN.
- Evidence of hepatitis B and/or positive hepatitis B surface antigen.
- Clinical symptoms associated with cholelithiasis (eg, cholecystitis or biliary colic), within 3 years of Visit 1 (Screening).
- History of, or currently have acute or chronic pancreatitis, or have triglyceride concentrations ≥500 mg/dL at Visit 1 (Screening).
- Have a serum calcitonin concentration ≥40 pg/mL at Visit 1 (Screening).
- An abnormality in the 12-lead ECG that, in the opinion of the PI, increases the risks associated with participating in the study.
- Evidence of significant active neuropsychiatric disease.
- Evidence of current use of drugs of abuse or history of use within the past year.
- Women who are lactating and/or breastfeeding.
- Use of over-the-counter or prescription medication (other than thyroid replacement therapy, metformin, antihypertensive medication, lipid-lowering agents, aspirin, or paracetamol/acetaminophen) 7 and 14 days, respectively prior to dosing. If this situation arises, inclusion of an otherwise suitable patient may occur if permitted by the PI and Sponsor.
- Significant active hematological disease and/or blood donation of more than 400 mL within the last 6 months.
- An average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females), or patients unwilling to adhere to study alcohol restrictions (1 unit=360 mL of beer; 150 mL of wine; 45 mL of distilled spirits).
- A personal or family history of medullary thyroid cancer or multiple endocrine neoplasia 2A or 2B.
- Currently enrolled in any other clinical study.
- Determined by the PI to be unsuitable for inclusion in this study.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single arm of exenatide once-weekly suspension
Arm Description
Exenatide once-weekly suspension via subcutaneous (SC) injection
Outcomes
Primary Outcome Measures
Plasma concentrations versus time profile of exenatide
To evaluate the PK of single and multiple doses of exenatide once-weekly suspension in native Chinese patients with T2DM
Cmax
Maximum plasma concentration directly from the observed concentration versus time data
tmax
Time of maximum plasma concentration
AUC(0-8h)
Area under the plasma concentration-time curve from zero (pre-dose) to time 8 h calculated by linear up/log down trapezoidal rule (following the first dose on Day 1)
AUC(0-168h)
Area under the plasma concentration-time curve from zero (pre-dose) to time 168 h calculated by linear up/log down trapezoidal rule (following the first dose on Day 1)
AUCτ,ss
Area under the plasma concentration-time curve over a dosing interval at steady state calculated by linear up/log down trapezoidal rule (following administration at Week 14)
Cav,ss
Average plasma concentration at steady state calculated as AUCτ ,ss/τ (following administration at Week 14)
λ z
Apparent terminal elimination rate constant (1/h) determined by linear regression of the terminal points of the log-linear concentration-time curve. Visual assessment will be used to identify the terminal linear phase of the concentration-time profile. A minimum of 3 data points and an Rsq of at least 0.800 will be used for determination. (following administration at Week 14)
t½
Apparent terminal half-life (h) determined as ln 2/λ z (following administration at Week 14)
CL/F
Apparent total body clearance (L/h) calculated as dose/AUCτ,ss (following administration at Week 14)
Vss/F
Apparent volume of distribution at steady state (following administration at Week 14)
Rac
Accumulation ratio calculated as AUCτ,ss/AUC0-168h
Ctrough
Trough plasma concentrations through the treatment period will be evaluated graphically to assess steady-state attainment
Secondary Outcome Measures
Electrocardiograms (ECGs)
Safety as determined by analysis of 12-lead ECG. Routine 12-lead ECG will be done during study including test of heart rate, rhythm, P wave, QRS, PR interval, ST-T, QT interval.
Blood pressure (BP)
Safety as determined by evaluation of supine blood pressure (systolic and diastolic) in mmHg.
Pulse rate
Safety as determined by evaluation of supine pulse rate in beats per minute.
Body temperature
Safety as determined by evaluation of body temperature in Celsius degrees.
Safety and tolerability as determined by abnormality in clinical chemistry compared to baseline.
Measurement of kidney function (e.g.urea, creatinine, Uric acid), liver function (ALP, ALT, AST, albumin, total bilirubin, direct bilirubin), lipid profile (total cholesterol, triglycerides, LDL, HDL), potassium and etc.
Safety and tolerability as determined by abnormality in hematology compared to baseline.
Measurement of red blood cell count, white blood cell count, haemoglobin and platelets
Safety and tolerability as determined by abnormality in urinalysis compared to baseline.
Measurement of leukocyte, red blood cells, protein and microscopy
Fasting blood glucose
Safety as determined by abnormality in blood glucose levels
Calcitonin
Calcitonin levels will be measured per the study plan to determine the possible effect of exenatide once-weekly suspension on thyroid function.
Number of subjects with adverse events
Following categories will be collected and analyzed: any adverse event (AE), any AE causally related to investigational product (IP), serious adverse events (SAEs), SAEs causally related to IP, AEs with outcome of death, AEs leading to discontinuation of IP, and other significant AEs.
The presence and titer of anti-exenatide antibodies
Historically, the small subset of exenatide concentrations associated with antibody titers >625 have been excluded from PK analyses due to evidence that these exenatide concentration measurements were unduly affected by negative interference from these antibodies in the exenatide bioanalytical method. Therefore the exenatide concentrations associated with antibody titers >625 may be excluded from the PK analysis.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04001231
Brief Title
Study of Exenatide Once-Weekly Suspension in Chinese Patients With Type 2 Diabetes Mellitus
Official Title
A Phase 1, Open-Label Study to Evaluate Single and Multiple Dose Pharmacokinetics, Safety, and Tolerability of Exenatide Once-Weekly Suspension in Chinese Patients With Type 2 Diabetes Mellitus
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Withdrawn
Why Stopped
The study is stopped based upon strategic considerations impacting the clinical development of exenatide once-weekly suspension in China
Study Start Date
June 30, 2020 (Anticipated)
Primary Completion Date
July 2, 2021 (Anticipated)
Study Completion Date
July 2, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the pharmacokinetics, tolerability, and safety of single and multiple doses of exenatide once-weekly suspension via subcutaneous (SC) injection using a pre-filled, single-dose autoinjector in male and female Chinese with type 2 diabetes.
Detailed Description
This is an open-label, single- and multiple-dose, PK study in Chinese subjects with type 2 diabetes mellitus. Up to 30 patients may initially be enrolled to target at least 20 patients completing the study. Up to 10 more patients (ie, 40 in total) may be subsequently recruited to replace patients who discontinue, provided such discontinuations are not due to significant (based on PI and Sponsor judgment) safety or tolerability issues. Eligible patients will receive their first 2.0-mg dose of exenatide once-weekly suspension via subcutaneous (SC) injection using a pre-filled, single-dose autoinjector at Visit 3 (Day 1).Blood samples will be drawn for up to 168 hours after the first dose on Day 1 to assess single-dose PK for exenatide once-weekly suspension. Patients will receive the second dose of the investigational product (IP) at Visit 6 (Day 8). Thereafter, patients will receive weekly (±1 day) doses of IP up to Visit 18 (Week 14). Intensive and extended PK sampling will be conducted after administration of the final dose (Dose 14) to assess multiple-dose PK for exenatide once-weekly suspension. Follow-up observations will be conducted at Visits 22 to 29 (Weeks 15 to 26), with the final follow-up at/after Visit 29 (Week 26 ±2 days). During follow-up period, Blood samples will be collected for PK analyses. Subjects will be monitored closely for adverse events throughout the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes
Keywords
Pharmacokinetics, Safety, Tolerability, exenatide once weekly, Chinese
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Single group
Masking
None (Open Label)
Masking Description
Open-label Study
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single arm of exenatide once-weekly suspension
Arm Type
Experimental
Arm Description
Exenatide once-weekly suspension via subcutaneous (SC) injection
Intervention Type
Drug
Intervention Name(s)
Exenatide Once-Weekly Suspension
Intervention Description
A single dose will be administered as 2.0-mg dose of exenatide onceweekly suspension via subcutaneous (SC) injection followed by blood samples be drawn for up to 168 hours after the first dose on Day 1 to assess single-dose PK for exenatide once-weekly suspension. Subsequently Patients will receive the second dose of the investigational product (IP) at Visit 6 (Day 8). Thereafter, patients will receive weekly (±1 day) doses of IP up to Visit 18 (Week 14).
Primary Outcome Measure Information:
Title
Plasma concentrations versus time profile of exenatide
Description
To evaluate the PK of single and multiple doses of exenatide once-weekly suspension in native Chinese patients with T2DM
Time Frame
Blood sample will be collected on Visit 3-6 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 7-17 (pre-dose). Visit 18-22 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 23-29 (once/visit).
Title
Cmax
Description
Maximum plasma concentration directly from the observed concentration versus time data
Time Frame
Blood sample will be collected on Visit 3-6 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 7-17 (pre-dose). Visit 18-22 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 23-29 (once/visit).
Title
tmax
Description
Time of maximum plasma concentration
Time Frame
Blood sample will be collected on Visit 3-6 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 7-17 (pre-dose). Visit 18-22 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 23-29 (once/visit).
Title
AUC(0-8h)
Description
Area under the plasma concentration-time curve from zero (pre-dose) to time 8 h calculated by linear up/log down trapezoidal rule (following the first dose on Day 1)
Time Frame
Blood sample will be collected on Visit 3-6 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 7-17 (pre-dose). Visit 18-22 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 23-29 (once/visit).
Title
AUC(0-168h)
Description
Area under the plasma concentration-time curve from zero (pre-dose) to time 168 h calculated by linear up/log down trapezoidal rule (following the first dose on Day 1)
Time Frame
Blood sample will be collected on Visit 3-6 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 7-17 (pre-dose). Visit 18-22 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 23-29 (once/visit).
Title
AUCτ,ss
Description
Area under the plasma concentration-time curve over a dosing interval at steady state calculated by linear up/log down trapezoidal rule (following administration at Week 14)
Time Frame
Blood sample will be collected on Visit 3-6 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 7-17 (pre-dose). Visit 18-22 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 23-29 (once/visit).
Title
Cav,ss
Description
Average plasma concentration at steady state calculated as AUCτ ,ss/τ (following administration at Week 14)
Time Frame
Blood sample will be collected on Visit 3-6 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 7-17 (pre-dose). Visit 18-22 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 23-29 (once/visit).
Title
λ z
Description
Apparent terminal elimination rate constant (1/h) determined by linear regression of the terminal points of the log-linear concentration-time curve. Visual assessment will be used to identify the terminal linear phase of the concentration-time profile. A minimum of 3 data points and an Rsq of at least 0.800 will be used for determination. (following administration at Week 14)
Time Frame
Blood sample will be collected on Visit 3-6 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 7-17 (pre-dose). Visit 18-22 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 23-29 (once/visit).
Title
t½
Description
Apparent terminal half-life (h) determined as ln 2/λ z (following administration at Week 14)
Time Frame
Blood sample will be collected on Visit 3-6 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 7-17 (pre-dose). Visit 18-22 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 23-29 (once/visit).
Title
CL/F
Description
Apparent total body clearance (L/h) calculated as dose/AUCτ,ss (following administration at Week 14)
Time Frame
Blood sample will be collected on Visit 3-6 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 7-17 (pre-dose). Visit 18-22 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 23-29 (once/visit).
Title
Vss/F
Description
Apparent volume of distribution at steady state (following administration at Week 14)
Time Frame
Blood sample will be collected on Visit 3-6 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 7-17 (pre-dose). Visit 18-22 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 23-29 (once/visit).
Title
Rac
Description
Accumulation ratio calculated as AUCτ,ss/AUC0-168h
Time Frame
Blood sample will be collected on Visit 3-6 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 7-17 (pre-dose). Visit 18-22 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 23-29 (once/visit).
Title
Ctrough
Description
Trough plasma concentrations through the treatment period will be evaluated graphically to assess steady-state attainment
Time Frame
Blood sample will be collected on Visit 3-6 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 7-17 (pre-dose). Visit 18-22 (pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 24, 72, 120, 168 hours post-dose). Visit 23-29 (once/visit).
Secondary Outcome Measure Information:
Title
Electrocardiograms (ECGs)
Description
Safety as determined by analysis of 12-lead ECG. Routine 12-lead ECG will be done during study including test of heart rate, rhythm, P wave, QRS, PR interval, ST-T, QT interval.
Time Frame
ECGs will be performed at Visit 1 (screening), Visit 3 (Day 1, pre-dose and 2 hours post-dose), Visit 18 (Week 14, Day 1, pre-dose and 2 hours post-dose) and Visit 29 (Week 26, follow-up)
Title
Blood pressure (BP)
Description
Safety as determined by evaluation of supine blood pressure (systolic and diastolic) in mmHg.
Time Frame
Blood pressure will be collected at Visit 1, Visit 3 (pre-dose, 2- and 24-hours post-dose), Visit 4 (post-dose), Visit 5 (post-dose), Visit 6-17 (pre-dose), Visit 18 (pre-dose, 2- and 24-hours post-dose), Visit 19-21 (post-dose), Visit 22-29
Title
Pulse rate
Description
Safety as determined by evaluation of supine pulse rate in beats per minute.
Time Frame
Pulse rate will be collected at Visit 1, Visit 3 (pre-dose, 2- and 24-hours post-dose), Visit 4 (post-dose), Visit 5 (post-dose), Visit 6-17 (pre-dose), Visit 18 (pre-dose, 2- and 24-hours post-dose), Visit 19-21 (post-dose), Visit 22-29
Title
Body temperature
Description
Safety as determined by evaluation of body temperature in Celsius degrees.
Time Frame
Body temperature will be collected at Visit 1, Visit 3 (pre-dose, 2- and 24-hours post-dose), Visit 4 (post-dose), Visit 5 (post-dose), Visit 6-17 (pre-dose), Visit 18 (pre-dose, 2- and 24-hours post-dose), Visit 19-21 (post-dose), Visit 22-29
Title
Safety and tolerability as determined by abnormality in clinical chemistry compared to baseline.
Description
Measurement of kidney function (e.g.urea, creatinine, Uric acid), liver function (ALP, ALT, AST, albumin, total bilirubin, direct bilirubin), lipid profile (total cholesterol, triglycerides, LDL, HDL), potassium and etc.
Time Frame
Blood sample will be collected at Visit 1 (screening), Visit 2 (admission, day -1), Visit 6 (Week2, pre-dose), Visit 8 (Week4, pre-dose), Visit 17 (Week13, pre-dose), Visit 23 (Week16, follow-up), Visit 29 (Week26, follow-up)
Title
Safety and tolerability as determined by abnormality in hematology compared to baseline.
Description
Measurement of red blood cell count, white blood cell count, haemoglobin and platelets
Time Frame
Blood sample will be collected at Visit 1 (screening), Visit 2 (admission, day -1), Visit 6 (Week2, pre-dose), Visit 8 (Week4, pre-dose), Visit 17 (Week13, pre-dose), Visit 23 (Week16, follow-up), Visit 29 (Week26, follow-up)
Title
Safety and tolerability as determined by abnormality in urinalysis compared to baseline.
Description
Measurement of leukocyte, red blood cells, protein and microscopy
Time Frame
Blood sample will be collected at Visit 1 (screening), Visit 2 (admission, day -1), Visit 6 (Week2, pre-dose), Visit 8 (Week4, pre-dose), Visit 17 (Week13, pre-dose), Visit 23 (Week16, follow-up), Visit 29 (Week26, follow-up)
Title
Fasting blood glucose
Description
Safety as determined by abnormality in blood glucose levels
Time Frame
Blood sample will be collected at Visit1, Visit3 (Day1, pre-dose), Visit4-5 (Day4, Day6, post-dose), Visit6-18 (Week2-14, pre-dose), Visit19 (Week14, Day4, post-dose) and Visit20 (Week14, Day6, post-dose), Visit22-26 (Week15-20) and Visit29 (Week26)
Title
Calcitonin
Description
Calcitonin levels will be measured per the study plan to determine the possible effect of exenatide once-weekly suspension on thyroid function.
Time Frame
Blood sample will be collected at Visit1 (screening), Visit21 (Week14, Day7) and Visit29 (Week26, follow-up)
Title
Number of subjects with adverse events
Description
Following categories will be collected and analyzed: any adverse event (AE), any AE causally related to investigational product (IP), serious adverse events (SAEs), SAEs causally related to IP, AEs with outcome of death, AEs leading to discontinuation of IP, and other significant AEs.
Time Frame
Adverse event will be collected from Visit 1 (screening) to Visit 29 (Week 26, follow-up).
Title
The presence and titer of anti-exenatide antibodies
Description
Historically, the small subset of exenatide concentrations associated with antibody titers >625 have been excluded from PK analyses due to evidence that these exenatide concentration measurements were unduly affected by negative interference from these antibodies in the exenatide bioanalytical method. Therefore the exenatide concentrations associated with antibody titers >625 may be excluded from the PK analysis.
Time Frame
Visit 3, Visit 6~18, Visit 21 and Visit 29 (once every visit)
Other Pre-specified Outcome Measures:
Title
HbA1c
Description
Exploratory evaluation of HbA1c after 2.0 mg exenatide given once weekly as a suspension in native Chinese patients with T2DM following single and multiple weekly SC injections
Time Frame
Blood sample will be collected at Visit1 (screening), Visit3 (Day1, pre-dose), Visit7 (Week 3, pre-dose), V10 (Week6, pre-dose), Visit13 (Week9, pre-dose), Visit16 (Week12, pre-dose), Visit21 (Week14, Day7, post-dose) and Visit29 (Week 26, follow-up)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Provision of informed consent prior to any study-specific procedures.
Male or female patients with T2DM treated with diet modification and exercise alone or in combination with a stable (in PI's opinion) regimen of metformin only for at least two months prior to screening. The T2DM diagnosis will be confirmed clinically by the PI, and should be consistent with the World Health Organization criteria for diagnosis and classification of diabetes
Between 20 to 75 years of age inclusive at Visit 1 (Screening)
The following criterion applies to females of child-bearing potential (not surgically sterilized and between menarche and 1-year postmenopause) only:
Test negative for pregnancy at the time of screening.
Intend not to become pregnant during the study.
Are sexually inactive or have practiced a reliable method of birth control (for example, use of oral contraceptives or levonorgestrel, diaphragms with contraceptive jelly, cervical caps with contraceptive jelly, condoms with contraceptive foam, intrauterine devices, partner with vasectomy) for at least 6 weeks prior to screening.
Agree to continue to use a reliable method of birth control (as determined by the PI) during the study and until 90 days after last dose.
Have a body weight of ≥45 kg and a body mass index (BMI) of 18.5 to 35 kg/m2 inclusive at Visit 1 (Screening).
Have clinical laboratory test results within the normal reference range for the population or study site, or with abnormalities deemed clinically insignificant by the PI. Abnormalities of plasma glucose (fasting ≤12.0 mmol/L and anytime≤15.0mmol/L), HbA1c (<10.5%), plasma lipids (TG<5.7 mmol/L), and urinary protein (with a range of trace < 2+ on dipstick) are acceptable.
Venous access sufficient to allow blood sampling as per the protocol.
Are reliable and willing to be available for the duration of the study and are willing to follow study procedures.
Exclusion Criteria:
Involvement in the planning and/or conduct of the study (applies to bothAstraZeneca staff and/or staff at the study site, and direct family members).
Previous enrollment in the present study or have previously completed or withdrawn from any other study investigating exenatide.
Within 30 days of the initial dose of IP, have received treatment with a drug that has not received regulatory approval for any indication.
Known allergy or hypersensitivity to exenatide or any of the excipients contained in these agents (exenatide: sodium acetate buffer, mannitol, metacresol, MCT vehicle).
Previous treatment with exenatide or related GLP-1 receptor agonist compounds.
History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, haematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data.
Systolic blood pressure (SBP) persistently (on ≥2 separate occasions) >160 mmHg on stable regimen of antihypertensive medication or >180 mmHg regardless of antihypertensive treatment.
History of, or currently have angina, revascularization, myocardial infarction, or heart failure.
Clinically significant peripheral vascular disease.
Evidence of poorly controlled T2DM or evidence of significant diabetes-related complications such as:
Plasma glucose >12 mmol/L (fasting) or >15 mmol/L (anytime) at Visit 1 (Screening)
HbA1c >10.5%
History of hypoglycemic or hyperglycemic coma within 1 year prior to Visit 1 (Screening)
History of active diabetic proliferative retinopathy or macular oedema
Known significant autonomic neuropathy as evidenced by urinary retention, orthostatic hypotension, diabetic diarrhea, or gastroparesis
Two or more episodes of major hypoglycemia within 6 months prior to Visit 1 (Screening). See Section 5.2.8.1 for hypoglycemia classification.
Impaired renal function (serum creatinine >125 μ/mol/L in women, >132 μ/mol/L in men).
Liver disease, acute or chronic hepatitis, alanine aminotransferase (ALT/SGPT), or aspartate aminotransferase (AST) ≥3x upper limit of normal (ULN) of the reference range and total bilirubin level (TBL) ≥2xULN.
Evidence of hepatitis B and/or positive hepatitis B surface antigen.
Clinical symptoms associated with cholelithiasis (eg, cholecystitis or biliary colic), within 3 years of Visit 1 (Screening).
History of, or currently have acute or chronic pancreatitis, or have triglyceride concentrations ≥500 mg/dL at Visit 1 (Screening).
Have a serum calcitonin concentration ≥40 pg/mL at Visit 1 (Screening).
An abnormality in the 12-lead ECG that, in the opinion of the PI, increases the risks associated with participating in the study.
Evidence of significant active neuropsychiatric disease.
Evidence of current use of drugs of abuse or history of use within the past year.
Women who are lactating and/or breastfeeding.
Use of over-the-counter or prescription medication (other than thyroid replacement therapy, metformin, antihypertensive medication, lipid-lowering agents, aspirin, or paracetamol/acetaminophen) 7 and 14 days, respectively prior to dosing. If this situation arises, inclusion of an otherwise suitable patient may occur if permitted by the PI and Sponsor.
Significant active hematological disease and/or blood donation of more than 400 mL within the last 6 months.
An average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females), or patients unwilling to adhere to study alcohol restrictions (1 unit=360 mL of beer; 150 mL of wine; 45 mL of distilled spirits).
A personal or family history of medullary thyroid cancer or multiple endocrine neoplasia 2A or 2B.
Currently enrolled in any other clinical study.
Determined by the PI to be unsuitable for inclusion in this study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Quanying Zhang
Organizational Affiliation
Second Affiliated Hospital of Suzhou University
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Study of Exenatide Once-Weekly Suspension in Chinese Patients With Type 2 Diabetes Mellitus
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