A Randomized, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of JNJ 28431754 on Cardiovascular Outcomes in Adult Subjects With Type 2 Diabetes Mellitus

Phase 3

Completed

• Conditions: diabetes; Diabetes mellitus; 10012653

• Registration Number: NL-OMON36405
• Lead Sponsor: Janssen-Cilag

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 6 May 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 300

Inclusion Criteria

Inclusion Criteria at Screening Visit
*Man or woman with a diagnosis of T2DM with HbA1c level > or <= 7.0% to < or <= 10.5% at screening and be either (1) not currently on AHA therapy or (2) on AHA monotherapy or combination therapy with any approved class of agents: eg, sulfonylurea, pioglitazon, metformin, PPAR* agonist, alpha-glucosidase inhibitor, GLP-1 analogue, DPP-4 inhibitor, or insulin.
*History or high risk of CV disease defined on the basis of either:
*Age > or <= 30 years with documented symptomatic atherosclerotic CV disease: including stroke; MI; hospital admission for unstable angina; coronary artery bypass graft; percutaneous coronary intervention (with or without stenting); peripheral revascularization (angioplasty or surgery); symptomatic with documented hemodynamically-significant carotid or peripheral vascular disease; or amputation secondary to vascular disease
*Age > or <= 50 years with 2 or more of the following risk factors determined at the screening visit: duration of T2DM of 10 years or more, systolic blood pressure >140 mmHg on at least one blood pressure-lowering treatment, current daily cigarette smoker, documented micro- or macro¬-albuminuria, or documented HDL-C of <1 mmol/L (<39 mg/dL).
Note: an overall 70%:30% target ratio for CV history (first category):risk factors (second category) will be implemented (with max 40% in 2nd category); this ratio is intended to be a global ratio and may vary by region.The proportion of subjects in these categories will be monitored centrally.
*Women must not be or get pregnant during their participation at the trial.
*Willing and able to adhere to the prohibitions and restrictions specified in this protocol
*Subjects must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study
*To participate in the optional pharmacogenomic component of this study, subjects must have signed the informed consent form for pharmacogenomic research indicating willingness to participate in the pharmacogenomic component of the study (where local regulations permit). Refusal to give consent for this component does not exclude a subject from participation in the clinical study.
Inclusion Criterion for Randomization: Subjects must have taken >80% of their single-blind placebo tablets during the 2 week run-in period at Day 1 to be eligible for randomization.

Exclusion Criteria

Diabetes-Related/Metabolic
*History of diabetic ketoacidosis, T1DM, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy
*On an AHA and not on a stable regimen (ie, agents and doses) for at least 8 weeks before the screening visit
Note: a stable dose of insulin is defined as no change in the insulin regimen (ie, type[s] of insulin) and < or = 10% change in the average total daily dose of insulin.
*Fasting fingerstick glucose at home or investigational site >270 mg/dL (>15 mmol/L) at Baseline/Day 1
*For patients on a sulphonylurea agent or on insulin: fasting fingerstick glucose at home or investigational site <110 mg/dL (<6 mmol/L) at Baseline/Day 1
Note: at the investigator*s discretion, based upon an assessment of recent SMBG values, subjects meeting either of these fingerstick glucose exclusion criteria may return to the investigational site within 14 days and be randomized if the repeat fasting fingerstick value no longer meets the criterion. Subjects with fingerstick glucose >270 mg/dL (>15 mmol/L) may have their AHA regimen adjusted, and be rescreened once on a stable regimen for at least 8 weeks.
*History of one or more severe hypoglycemic episode within 6 months before screening
*History of hereditary glucose-galactose malabsorption or primary renal glucosuria
*Run-in visit thyroid stimulating hormone [TSH] value that is <0.2 or >10 mIU/L. Subjects taking a thyroxine supplementation for thyroid disorder should be on a stable dose for at least 6 weeks before baseline
Renal/Cardiovascular
*Renal disease that required treatment with immunosuppressive therapy or a history of chronic dialysis or renal transplant. Note: subjects with a history of treated childhood renal disease, without sequelae, may participate
*Myocardial infarction, unstable angina, revascularization procedure, or cerebrovascular accident within 3 months before screening, or a planned revascularization procedure, or history of New York Heart Association (NYHA) Class IV cardiac disease; refer to Attachment 3, New York Heart Association Classification of Cardiac Disease, for a description of the classes
*Findings on 12-lead ECG that would require urgent diagnostic evaluation or intervention (eg, new clinically important arrhythmia or conduction disturbance)
Gastrointestinal
*History of hepatitis B surface antigen or hepatitis C antibody positive (unless associated with documented persistently stable/normal range aspartate aminotransferase [AST] and ALT levels), or other clinically active liver disease
*Any history of or planned bariatric surgery
Laboratory
*Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 at screening (provided by the central laboratory)
*For subjects taking metformin: serum creatinine > or = 1.5 mg/dL (133 *mol/L) for men and > or = 1.4 mg/dL (124 µmol/L) for women, at screening; or eGFR <60 mL/min/1.73m2, at screening
*ALT levels >2.0 times the ULN or total bilirubin >1.5 times the ULN, at screening, unless in the opinion of the investigator and as agreed upon by the sponsor*s medical officer, the findings are consistent with Gilbert*s disease
Other conditions
*History of malignancy within 5 years before screening (exceptions: squamous and basal cell carcinomas of the skin and carcinoma of the cervix in situ, or a malignancy that in the opinion of the investigator, with concurrence with the sponsor*s medi

Study & Design

• Study Type: Interventional
• Study Design: Not specified