Study of Exenatide Once-Weekly Suspension in Chinese Patients with Type 2 Diabetes Mellitus

Study identifier:D5553C00008

ClinicalTrials.gov identifier:NCT04001231

EudraCT identifier:N/A

CTIS identifier:N/A

Terminated/Withdrawn

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

Medical condition

Type 2 Diabetes

Phase

Phase 1

Healthy volunteers

Study drug

Exenatide Once-Weekly Suspension

Sex

All

Actual Enrollment

Study type

Interventional

Age

20 Years - 75 Years

Date

Study Start Date: 30 Jun 2020

Estimated Primary Completion Date: 02 Jul 2021

Estimated Study Completion Date: 02 Jul 2021

Study design

Allocation: N/A
Endpoint Classification: -
Intervention Model: Single Group Assignment
Masking: -
Primary Purpose: Other

Verification:

Verified 01 May 2020 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

1. Provision of informed consent prior to any study-specific procedures.
2. 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
3. Between 20 to 75 years of age inclusive at Visit 1 (Screening)
4. The following criterion applies to females of child-bearing potential (not surgically sterilized and
between menarche and 1-year postmenopause) only:
(a) Test negative for pregnancy at the time of screening.
(b) Intend not to become pregnant during the study.
(c) 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.
(d) 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.
5. 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).
6. 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.
7. Venous access sufficient to allow blood sampling as per the protocol.
8. Are reliable and willing to be available for the duration of the study and are willing to follow study
procedures.

Exclusion Criteria

1. 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).
2. Previous enrollment in the present study or have previously completed or withdrawn from any other
study investigating exenatide.
3. Within 30 days of the initial dose of IP, have received treatment with a drug that has not received
regulatory approval for any indication.
4. Known allergy or hypersensitivity to exenatide or any of the excipients contained in these agents
(exenatide: sodium acetate buffer, mannitol, metacresol, MCT vehicle).
5. Previous treatment with exenatide or related GLP-1 receptor agonist compounds.
6. 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.
7. Systolic blood pressure (SBP) persistently (on ≥2 separate occasions) >160 mmHg on stable
regimen of antihypertensive medication or >180 mmHg regardless of antihypertensive treatment.
8. History of, or currently have angina, revascularization, myocardial infarction, or heart failure.
9. Clinically significant peripheral vascular disease.
10. Evidence of poorly controlled T2DM or evidence of significant diabetes-related complications such
as:
(a) Plasma glucose >12 mmol/L (fasting) or >15 mmol/L (anytime) at Visit 1 (Screening)
(b) HbA1c >10.5%
(c) History of hypoglycemic or hyperglycemic coma within 1 year prior to Visit 1 (Screening)
(d) History of active diabetic proliferative retinopathy or macular oedema
(e) Known significant autonomic neuropathy as evidenced by urinary retention, orthostatic
hypotension, diabetic diarrhea, or gastroparesis
11. Two or more episodes of major hypoglycemia within 6 months prior to Visit 1 (Screening). See
Section 5.2.8.1 for hypoglycemia classification.
12. Impaired renal function (serum creatinine >125 μ/mol/L in women, >132 μ/mol/L in men).
13. 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.
14. Evidence of hepatitis B and/or positive hepatitis B surface antigen.
15. Clinical symptoms associated with cholelithiasis (eg, cholecystitis or biliary colic), within 3 years of
Visit 1 (Screening).
16. History of, or currently have acute or chronic pancreatitis, or have triglyceride concentrations ≥500
mg/dL at Visit 1 (Screening).
17. Have a serum calcitonin concentration ≥40 pg/mL at Visit 1 (Screening).
18. An abnormality in the 12-lead ECG that, in the opinion of the PI, increases the risks associated with
participating in the study.
19. Evidence of significant active neuropsychiatric disease.
20. Evidence of current use of drugs of abuse or history of use within the past year.
21. Women who are lactating and/or breastfeeding.
22. 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.
23. Significant active hematological disease and/or blood donation of more than 400 mL within the last
6 months.
24. 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).
25. A personal or family history of medullary thyroid cancer or multiple endocrine neoplasia 2A or 2B.
26. Currently enrolled in any other clinical study.
27. Determined by the PI to be unsuitable for inclusion in this study.

No locations available

Arms	Assigned Interventions
Experimental: Single arm of exenatide once-weekly suspension Exenatide once-weekly suspension via subcutaneous (SC) injection	Drug: Exenatide Once-Weekly Suspension 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).

Arms

Assigned Interventions

Experimental: Single arm of exenatide once-weekly suspension
Exenatide once-weekly suspension via subcutaneous (SC) injection

Drug: Exenatide Once-Weekly Suspension
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).

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

Quanying Zhang

Second Affiliated Hospital of Suzhou University