Chinese Multiple Dose Escalation (MDE) High Dose Study

• Status: Recruiting
• Trial end date: 2022-11-30
• Target enrollment: 0
• Participant gender: All

Summary

A Phase 1 Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Cotadutide in Overweight/Obese Subjects with Chinese ancestry with Type 2 Diabetes Mellitus

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AstraZeneca

Criteria

Inclusion Criteria:

• Subjects aged 18 to 74 years

• Provision of signed and dated written informed consent prior to any study specific procedures

• BMI between 25 and 35 kg/m2

• HbA1c range of 7% to 8.5%

• Willing and able to self-inject investigational product

• Diagnosed with T2DM with glucose control managed with metformin monotherapy where no significant dose change (increase or decrease ≥ 500 mg/day) has occurred in the three months prior to screening

• Women of child-bearing potential who are sexually active with a male partner must be using at least one highly effective method of contraception from screening and up to 4 weeks after the last dose of IP. Women of child-bearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the start of IP, and must not be breastfeeding

Exclusion Criteria:

• History of, or any existing condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product, put the subject at risk, influence the subject's ability to participate or affect the interpretation of the results of the study and/or any subject unable or unwilling to follow study procedures

• Any subject who has received another investigational product as part of a clinical study or a GLP-1 analogue containing preparation within the last 30 days or 5 half-lives of the drug at the time of screening

• Participation in another randomization study of any kind, repeat randomization in this study is prohibited

• Any subject who has received any of the following medications within the specified timeframe prior to the start of the study (see Section 6.5.2 for further details)

• Herbal preparations for control of body weight or appetite within one week prior to the prior to the start of screening

• Drugs licensed for control of body weight or appetite (e.g., orlistat, bupropionnaltrexone, phentermine-topiramate, phentermine, lorcaserin) within 30 days (or 5 half-lives of the drug, Whichever is longer) prior to the start of screening

• Opiates, domperidone, metoclopramide, or other drugs known to alter gastric emptying

• Antimicrobials within the quinolone (eg, ciprofloxacin), macrolide (eg, clarithromycin) or azole class (eg, ketoconazole)

• Any change in antihypertensive medication

• Aspirin (acetylsalicylic acid) at a dose greater than 150 mg once daily

• Paracetamol (acetaminophen) or paracetamol-containing preparations at a total daily dose of greater than 3000 mg

• Ascorbic acid (vitamin C) supplements at a total daily dose of greater than 1000 mg

• Symptoms of acutely decompensated blood glucose control (eg, thirst, polyuria, weight loss), recent severe hypoglycemia, a history of type 1 diabetes mellitus or diabetic ketoacidosis

• Acute pancreatitis (pancreatic amylase > 1000 IU/L and/or pancreatic lipase > 600 IU/L) at screening or history of acute pancreatitis or chronic pancreatitis or serum triglyceride levels > 11 mmol/L (1000 mg/dL) at screening

• Significant inflammatory bowel disease gastroparesis or other severe disease or surgery affecting the upper GI tract which may affect gastric emptying or could affect the interpretation of safety and tolerability data

• Significant hepatic disease (except for NASH or non-alcoholic fatty liver disease without portal hypertension or cirrhosis) and/or subjects with any of the following results at screening:

• Aspartate transaminase (AST) ≥ 3 × upper limit of normal (ULN)

• Alanine transaminase (ALT) ≥ 3 × ULN

• Total bilirubin (TBL) ≥ 2 × ULN

• Impaired renal function defined as estimated glomerular filtration rate (GFR) < 30 mL/minute/1.73m2 at screening (GFR estimated according to Modification of Diet in Renal Disease (MDRD) using MDRD Study Equation IDMS-traceable [SI units]).

• Poorly controlled hypertension defined as:

• Systolic BP > 160 mmHg

• Diastolic BP or ≥ 90 mmHg After 10 minutes of supine rest and confirmed by repeated measurement at screening. Subjects who fail BP screening criteria may be considered for 24-hour ABPM at the discretion of the investigator. Subjects who maintain a mean 24-hour BP < 160/100 mmHg with a preserved nocturnal dip of > 15% will be considered eligible.

• Any clinically important abnormalities in rhythm, conduction, or morphology of the resting 12-lead ECG or any abnormalities that may interfere with the interpretation of serial ECG changes including corrected QT (QTc) interval changes , as judged by the investigator, and prolonged QT intervals corrected for heart rate using Fridericia's formula (QTcF) > 450 ms, or family history of long QT-segment at screening

• PR (PQ) interval prolongation (> 220 msec), intermittent second (Wenckebach block while asleep is not exclusive), or third-degree atrioventricular (AV) block, or AV dissociation

• Persistent or intermittent complete bundle branch block. Subjects with QRS > 110 msec but < 115 msec are acceptable if there is no evidence of ventricular hypertrophy or pre-excitation

• Unstable angina pectoris, myocardial infarction, transient ischemic attack, or stroke within 3 months prior to screening, or subjects who have undergone percutaneous coronary intervention or a coronary artery bypass graft within the past 6 months or who are due to undergo these procedures at the time of screening

• Severe congestive heart failure (New York Heart Association Class III or IV)

• Basal calcitonin level ≥ 50 ng/L at screening or history/family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN2)

• History of neoplastic disease within 5 years prior to screening, except for adequately treated basal cell, squamous cell skin cancer, or in situ cervical cancer

• Symptoms of depression or any other psychiatric disorder requiring treatment with medication However, subjects who use benzodiazepines for chronic anxiety or sleep disorders may be permitted to enter the study

• History of severe allergy/hypersensitivity

• Blood/plasma donation within 1 month

• For women only- currently pregnant or breastfeeding

• Any positive results for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody

• History of substance dependence, alcohol abuse, or excessive alcohol intake within 3 years