Clinical Trials/NCT04001231

NCT04001231

Withdrawn

Phase 1

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

AstraZeneca0 sitesJune 30, 2020

ConditionsType 2 Diabetes

InterventionsExenatide Once-Weekly Suspension

DrugsExenatide Once-Weekly Suspension

Overview

Phase: Phase 1
Intervention: Exenatide Once-Weekly Suspension
Conditions: Type 2 Diabetes
Sponsor: AstraZeneca
Primary Endpoint: AUC(0-8h)
Status: Withdrawn
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

June 30, 2020

End Date

July 2, 2021

Last Updated

5 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

AstraZeneca

Responsible Party

Sponsor

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.

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:

Arms & Interventions

Single arm of exenatide once-weekly suspension

Exenatide once-weekly suspension via subcutaneous (SC) injection

Intervention: Exenatide Once-Weekly Suspension

Outcomes

Primary Outcomes

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)

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)

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

CL/F

Apparent total body clearance (L/h) calculated as dose/AUCτ,ss (following administration at Week 14)

Cmax

Maximum plasma concentration directly from the observed concentration versus time data

Vss/F

Apparent volume of distribution at steady state (following administration at Week 14)

tmax

Time of maximum plasma concentration

Cav,ss

Average plasma concentration at steady state calculated as AUCτ ,ss/τ (following administration at Week 14)

Rac

Accumulation ratio calculated as AUCτ,ss/AUC0-168h

t½

Apparent terminal half-life (h) determined as ln 2/λ z (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)

Ctrough

Trough plasma concentrations through the treatment period will be evaluated graphically to assess steady-state attainment

Secondary Outcomes

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