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

A Phase 1 study testing Exenatide Once-Weekly Suspension in people with Type 2 Diabetes, run by AstraZeneca.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Trial 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. Read more about this study

Who is it for?: Ages 20 to 75 years
Conditions the study is for: Type 2 Diabetes
What is being tested?: Exenatide Once-Weekly Suspension
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: No sites listed yet
Study dates: 30 Jun 2020to 2 Jul 2021
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

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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.

Who cannot join

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.

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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.

About this study

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

Read the 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.

Conditions: Type 2 Diabetes
Being tested: Exenatide Once-Weekly Suspension
Keywords: Pharmacokinetics, Safety, Tolerability, exenatide once weekly, Chinese
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Exenatide Once-Weekly SuspensionDrug
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).

Study groups in NCT04001231
Study group	Role	What they receive
Single arm of exenatide once-weekly suspension	Experimental	Exenatide once-weekly suspension via subcutaneous (SC) injection Receives: Drug: Exenatide Once-Weekly Suspension

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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).
Cmax
Maximum plasma concentration directly from the observed concentration versus time data
Measured: 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).
tmax
Time of maximum plasma concentration
Measured: 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).
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)
Measured: 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).
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)
Measured: 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).
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)
Measured: 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).
Cav,ss
Average plasma concentration at steady state calculated as AUCτ ,ss/τ (following administration at Week 14)
Measured: 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).
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)
Measured: 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).
t½
Apparent terminal half-life (h) determined as ln 2/λ z (following administration at Week 14)
Measured: 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).
CL/F
Apparent total body clearance (L/h) calculated as dose/AUCτ,ss (following administration at Week 14)
Measured: 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).
Vss/F
Apparent volume of distribution at steady state (following administration at Week 14)
Measured: 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).
Rac
Accumulation ratio calculated as AUCτ,ss/AUC0-168h
Measured: 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).
Ctrough
Trough plasma concentrations through the treatment period will be evaluated graphically to assess steady-state attainment
Measured: 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 outcomes (11)

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.
Measured: 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)
Blood pressure (BP)
Safety as determined by evaluation of supine blood pressure (systolic and diastolic) in mmHg.
Measured: 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
Pulse rate
Safety as determined by evaluation of supine pulse rate in beats per minute.
Measured: 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
Body temperature
Safety as determined by evaluation of body temperature in Celsius degrees.
Measured: 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
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.
Measured: 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)
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
Measured: 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)
Safety and tolerability as determined by abnormality in urinalysis compared to baseline.
Measurement of leukocyte, red blood cells, protein and microscopy
Measured: 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)
Fasting blood glucose
Safety as determined by abnormality in blood glucose levels
Measured: 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)
Calcitonin
Calcitonin levels will be measured per the study plan to determine the possible effect of exenatide once-weekly suspension on thyroid function.
Measured: Blood sample will be collected at Visit1 (screening), Visit21 (Week14, Day7) and Visit29 (Week26, follow-up)
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.
Measured: Adverse event will be collected from Visit 1 (screening) to Visit 29 (Week 26, follow-up).
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.
Measured: Visit 3, Visit 6~18, Visit 21 and Visit 29 (once every visit)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Jun 20202 Jul 2021

First posted28 Jun 2019
Study start30 Jun 2020 (estimated)
Primary completion2 Jul 2021 (estimated)
Study completion2 Jul 2021 (estimated)

Why it stopped: The study is stopped based upon strategic considerations impacting the clinical development of exenatide once-weekly suspension in China

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Model description: Single group
Masking: None (open label)
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04001231
Sponsor's protocol ID: D5553C00008
Status last verified: May 2020
First submitted: 7 May 2019
Last updated: 4 Jun 2020
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Undecided

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Type 2 Diabetes trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT04001231
Acronym / sponsor ID: D5553C00008
Conditions: Type 2 Diabetes
Keywords: Pharmacokinetics, Safety, Tolerability, exenatide once weekly, Chinese
Phase: Phase 1
Study type: Interventional
Recruitment status: WithdrawnReason stopped: The study is stopped based upon strategic considerations impacting the clinical development of exenatide once-weekly suspension in China
Enrolment: 0 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: 30 Jun 2020 (estimated)
Primary completion: 2 Jul 2021 (estimated)
Study completion: 2 Jul 2021 (estimated)
First posted: 28 Jun 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Single group

Arm	Type	Receives
Single arm of exenatide once-weekly suspension	Experimental	Drug: Exenatide Once-Weekly SuspensionExenatide once-weekly suspension via subcutaneous (SC) injection

Who may qualify

Ages: 20 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

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:
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).

Key exclusion criteria (32 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Exenatide Once-Weekly SuspensionA 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).	Drug	Single arm of exenatide once-weekly suspension

Primary outcome

Plasma concentrations versus time profile of exenatide
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).
To evaluate the PK of single and multiple doses of exenatide once-weekly suspension in native Chinese patients with T2DM
Cmax
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).
Maximum plasma concentration directly from the observed concentration versus time data
tmax
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).
Time of maximum plasma concentration
AUC(0-8h)
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).
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)
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).
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
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).
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
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).
Average plasma concentration at steady state calculated as AUCτ ,ss/τ (following administration at Week 14)
λ z
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).
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
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).
Apparent terminal half-life (h) determined as ln 2/λ z (following administration at Week 14)
CL/F
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).
Apparent total body clearance (L/h) calculated as dose/AUCτ,ss (following administration at Week 14)
Vss/F
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).
Apparent volume of distribution at steady state (following administration at Week 14)
Rac
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).
Accumulation ratio calculated as AUCτ,ss/AUC0-168h
Ctrough
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).
Trough plasma concentrations through the treatment period will be evaluated graphically to assess steady-state attainment

11 secondary outcomes

Electrocardiograms (ECGs)
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)
Blood pressure (BP)
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
Pulse rate
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
Body temperature
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
Safety and tolerability as determined by abnormality in clinical chemistry compared to baseline.
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)
Safety and tolerability as determined by abnormality in hematology compared to baseline.
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)
Safety and tolerability as determined by abnormality in urinalysis compared to baseline.
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)
Fasting blood glucose
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)
Calcitonin
Time frame: Blood sample will be collected at Visit1 (screening), Visit21 (Week14, Day7) and Visit29 (Week26, follow-up)
Number of subjects with adverse events
Time frame: Adverse event will be collected from Visit 1 (screening) to Visit 29 (Week 26, follow-up).
The presence and titer of anti-exenatide antibodies
Time frame: Visit 3, Visit 6~18, Visit 21 and Visit 29 (once every visit)

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2020.
Individual participant dataSharing planned: Undecided

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Quanying Zhang principal investigator

Second Affiliated Hospital of Suzhou University

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Exenatide Once-Weekly Suspension in people with Type 2 Diabetes, run by AstraZeneca.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 4 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Plasma concentrations versus time profile of exenatide (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).). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04001231.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2020.