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

NCT04001231 | Withdrawn Phase 1

• 1 other identifier: D5553C00008
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Type 2 Diabetes

Keywords

Pharmacokinetics; Safety; Tolerability; exenatide once weekly; Chinese

Outcome Measures

Primary Outcomes (13)

• 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

  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

  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

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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

  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

  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)

  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)

  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

  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)

Other Outcomes (1)

• HbA1c

  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)

Study Arms (1)

Single arm of exenatide once-weekly suspension

EXPERIMENTAL

Exenatide once-weekly suspension via subcutaneous (SC) injection

Drug: Exenatide Once-Weekly Suspension

Interventions

Exenatide Once-Weekly Suspension DRUG

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).

Single arm of exenatide once-weekly suspension

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Quanying Zhang

  Second Affiliated Hospital of Suzhou University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open-label Study
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single group

Study Record Dates

• First Submitted: May 7, 2019
• First Posted: June 28, 2019
• Study Start: June 30, 2020
• Primary Completion: July 2, 2021
• Study Completion: July 2, 2021
• Last Updated: June 4, 2020

Record last verified: 2020-05