E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 Diabetes Mellitus in subjects with insufficient glycemic control on a stable dose of metformin |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluate the safety and tolerabililty of CCX140-B in subjects with Type 2 diabetes mellitus (T2DM) based on incidence of adverse events
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E.2.2 | Secondary objectives of the trial |
Evaluation of the effect of CCX140-B, compared to placebo, on: 1. Fasting plasma glucose concentrations; 2. Glucose tolerance, measured by an oral glucose tolerance test (OGTT); 3. Homeostasis model assessment of insulin resistance (HOMA-IR); 4. Fasting plasma insulin concentrations; 5. Glucose control based on HbA1c and fasting plasma fructosamine concentrations; 6. Serum total adiponectin concentrations; 7. Plasma monocyte chemoattractant protein-1 (MCP-1) concentrations; 8. Serum high sensitivity C-reactive protein (hsCRP) concentrations; 9. Serum lipid concentrations, including total cholesterol, high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides, and non-esterified fatty acids (NEFAs);
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male, postmenopausal (at least 2 years) or surgically sterile female subjects, aged 18-70 years inclusive, with type 2 diabetes mellitus; Male subjects with partners of childbearing potential may participate in the study if they had a vasectomy at least 6 months prior to randomization or they are using double-barrier contraception or barrier-method plus another method of contraception and continue to use one of these contraceptive methods throughout the study period; 2. Must have a body mass index ≥25 and <45 kg/m^2, but if body mass index is ≥25 and <28 kg/m^2, then waist circumference must be >94 cm for men and >80 cm for women; 3. Must be on a stable dose of metformin for at least 8 weeks prior to randomization; 4. If on lipid lowering agents, must be on stable doses for at least 4 weeks prior to randomization; 5. If on thyroid replacement therapy, the subject must be on a stable dose for at least 6 weeks prior to randomization, and the thyroid stimulating hormone (TSH) level must not be > 1.5 x upper limit of normal; 6. HbA1c of 6.5 to 10.0% inclusive and fasting plasma glucose 135 to 270 mg/dL inclusive at Screening; 7. Willing and able to give written Informed Consent and to comply with the requirements of the study protocol; and 8. Judged to be otherwise healthy by the Investigator, based on medical history, physical examination (including electrocardiogram [ECG]), and clinical laboratory assessments. Subjects with clinical laboratory values that are outside of normal limits (other than those specified in the Exclusion Criteria) and/or with other abnormal clinical findings that are judged by the Investigator not to be of clinical significance, may be entered into the study
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E.4 | Principal exclusion criteria |
1. Type 1 diabetes mellitus or history of diabetic ketoacidosis or other severe secondary diseases related to diabetes such as diabetic retinopathy, nephropathy, or diabetic foot; 2. Received insulin treatment within 12 weeks of randomization; 3. Received chronic (more than 7 days) systemic glucocorticoid treatment within 12 weeks of randomization; 4. Received sulfonylurea, thiazolidinedione, exenatide, or any other glucose lowering treatment (other than metformin) within 8 weeks of randomization; 5. Cardiac failure or history of cardiac failure (New York Heart Association [NYHA] stages I to IV), clinically evident peripheral edema, poorly-controlled hypertension (systolic blood pressure >160 or diastolic blood pressure >100), history of unstable angina, symptomatic coronary artery disease, myocardial infarction or stroke within 6 months of randomization, or chronic renal failure; 6. History of hypersensitivity or intolerance to any thiazolidinedione or to other peroxisome proliferator-activated receptor (PPAR) agonists, ingredients of the placebo (tartrazine, microcrystalline cellulose, starch, or croscarmellose sodium), or have previously received the active ingredient, CCX140-B; 7. History or presence of drug-induced myopathy, drug-induced creatine kinase elevation, or leukopenia (WBC count <3.5 x ((10^9)/L); 8. History or presence of any form of cancer within the 5 years prior to randomization, with the exception of excised basal cell or squamous cell carcinoma of the skin, or cervical carcinoma in situ or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis; 9. Presence of tuberculosis based on chest X rays, tuberculin skin test, QuantiFERON^®-TB Gold test, or T-SPOT^®.TB test performed during screening; 10. Positive HBV, HCV, or HIV viral screening test; 11. History of nervous system disease, including meningitis, epilepsy, multiple sclerosis or other neurodegenerative diseases, peripheral neuropathy, or gastroparesis; 12. Any infection requiring antibiotic treatment within 4 weeks of randomization; 13. Hemoglobin less than 11 g/dL (or 6.8 mmol/L) at Screening; 14. Evidence of hepatic disease; AST, ALT, alkaline phosphatase, or bilirubin > 2 x the upper limit of normal; 15. Evidence of renal impairment; serum creatinine ≥ 1.4 mg/dL for women or ≥ 1.5 mg/dL for men, or estimated Glomerular Filtration Rate (GFR) based on the Cockcroft-Gault equation < 60 mL/min; 16. Fasting serum triglyceride >400 mg/dL; 17. Clinically significant abnormal ECG during screening, e.g., QTc greater than 450 msec; 18. Participated in any clinical study of an investigational product within 30 days prior to randomization; and 19. History or presence of any medical condition or disease which, in the opinion of the Investigator, may place the subject at unacceptable risk for study participation
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E.5 End points |
E.5.1 | Primary end point(s) |
Subject incidence of adverse events. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |