A Randomised, Placebo-controlled, Double-blind, Semi-sequential Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Repeated Escalating Subcutaneous Doses of Glutazumab in Subjects with Type 2 Diabetes
Gmax Biopharm Australia Pty Ltd
44 participants
Oct 30, 2017
Interventional
Conditions
Summary
This study will be a multi-centre, double-blind, semi-sequential group, placebo-controlled, dose-escalation study to assess the safety, tolerability and PK/PD of glutazumab in subjects with T2D. After Screening, subjects will undergo a 4-week single-blind run-in period. All background diabetes medication will be kept constant. At the end of the single-blind run-in period, subjects will be randomised 3:1 to receive either glutazumab or placebo, and the 8-week double-blind treatment period will begin. Glycaemic control, Change frome baseline in body weight, Adverse events of special interest(AESIs) will be assessed. Pharmacodynamics and pharmacokinetics results will be collected.
Eligibility
Inclusion Criteria12
- Type 2 Diabetes diagnosed >6 months ago and controlled with diet or exercise alone or on stable doses of 1 or 2 of the following classes of OAMs:
- Metformin; Sulfonylureas;Glinides; Thiazolidinediones; Acarbose.
- If more than 2 of the permitted OAMs listed above are taken at Screening a wash-out period of 3 weeks will be needed.
- Body Mass Index (BMI) greater than or equal to 27 kg/m squared2 and less than or equal to 40 kg/m squared2
- Glycated haemoglobin (HbA1c) greater than or equal to 6.5% and less than or equal to 10.5%
- Fasting C-peptide greater than or equal to 0.8 ng/mL (greater than or equal to 0.26 nmol/L)
- Lipids, untreated or controlled with lipid-lowering drugs:
- a. Total cholesterol less than 200 mg/dL
- b. Low-density lipoprotein less than 100 mg/dL
- c. Fasting triglyceride level less than 400 mg/dL
- Females must be non-lactating
- Females or female partners of male study subjects must be surgically sterile or at least 2-years postmenopausal, or if of childbearing potential, have a negative urine pregnancy test at Screening and be willing to practice sexual abstinence or use an accepted form of contraception with her partner during treatment and for at least 30 days following the last dose of study drug.
Exclusion Criteria12
- Type 1 diabetes
- Any insulin use within 30 days prior to Screening or less than 7 days of consecutive insulin use in the 3 months prior to Screening
- Clinically significant cardiovascular and/or cerebrovascular diseases including, but not limited to stroke or transient ischemic attack, Active, unstable coronary heart disease, Unstable angina etc.
- Clinically significant laboratory abnormalities, including but not limited to Bilirubin, Aspartate aminotransferase (AST), glomerular filtration rate, etc.
- Lipase and amylase at Screening > upper limit of normal (ULN)
- History of acute or chronic liver disease
- Positive hepatitis B surface antigen or positive hepatitis C virus testing or positive for HIV
- Currently ongoing symptomatic biliary disease or history of acute/chronic pancreatitis.
- Poorly controlled hyperthyroidism (thyroid-stimulating hormone greater than 2 times ULN).
- Use of any GLP-1 analogue and/or DPP4 inhibitor within the last 30 days.
- Significant allergies to humanised monoclonal antibodies or allergies to other components of the study medication
- Females who are pregnant or breast-feeding and subjects of both sexes of childbearing potential who are not willing to use adequate contraceptive methods.
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Interventions
This study will be a multi-centre, double-blind, semi-sequential group, placebo-controlled, doseescalation study to assess the safety, tolerability and PK/PD of glutazumab in subjects with T2D. Four sequential cohorts, each with 6 subjects receiving glutazumab and 2 subjects receiving placebo, will be given increasing doses of glutazumab once weekly for 8 weeks (8 SC injections). The doses administered will be 5, 10, 20, and 30 mg once weekly. Prior to each dose escalation a Safety Review Committee (SRC) will meet to confirm the next dose level. A next dose level can only be started when all subjects in the preceding dose level have completed 4 weeks of dosing. Based on safety and PK data of these subjects a fifth cohort will be treated with a dose of glutazumab that will be determined by the SRC to be the most promising based on a risk-benefit evaluation. After Screening, subjects will undergo a 4-week single-blind run-in period. All background diabetes medication will be kept constant. At the end of the single-blind run-in period, subjects will be randomised 3:1 to receive either glutazumab or placebo, and the 8-week double-blind treatment period will begin. During the study, subjects will be reimbursed for their meals, parking during their visits, and investigator and research nurses will keep in close contact with subjects by weekly phone call and regular email to ensure the adherence to the study .
Locations(5)
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ACTRN12617000811303