E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Impaired Glucose Tolerance - Type 2 Diabetes |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II 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 |
The primary objective is to evaluate canakinumab effects on change from baseline of meal challenge derived insulin secretion rate relative to glucose 0-2 hours (Φd), at 4 weeks, on the following populations: a. patients with T2DM pre-treated and continuing on stable metformin monotherapy b. patients with T2DM pre-treated and continuing on a stable metformin dose in combination with a sulfonylurea c. metformin in combination with a sulfonylurea and a thiazolidinedione d. treatment with at least two insulin injections a day with or without metformin e. in patients with impaired glucose tolerance (IGT) |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to: 1. evaluate the effect on the populations stated in the primary objective on change from baseline of meal challenge derived parameters, Φs, Φtotal, insulin sensitivity index, glucose disposition indices, area under curve of time glucose concentration and glycemic control parameters 2. evaluate canakinumab effects on change from baseline of meal challenge derived parameters as a function of baseline meal challenge glucose parameters including PPG and maximal glycemic excursion 3. provide proof of principle for improving post prandial and impaired fasting glucose in people with IGT as measured by Φd 4. compare the change from baseline of Φd between ACZ885 and placebo in the IGT population 5. assess the safety and tolerability of ACZ885 vs. placebo as an add-on regimen over 4 weeks in patients with T2DM on the populations stated in the primary objective 6. PLS SEE PROTOCOL |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria: Patients eligible for inclusion in this study have to fulfill all of the following criteria during the Screening Period: 1. Patients must give written informed consent before any study related procedures are performed. 2. Patient must fulfill all criteria in one of the following groups: a. Impaired Glucose Tolerance (IGT) as defined by WHO criteria confirmed during the Screening Visit. o Morning fasting plasma glucose concentration less than 126 mg/dl (7.0 mmol/l) o Two hour plasma glucose concentration from Oral Glucose Tolerance Test (OGTT) of 75 g oral glucose ingestion greater than 140 mg/dl (7.8 mmol/l), but less than 200 mg/dl (11.1 mmol/l) o Will not be started on an anti-diabetic medicine during the course of screening/run-in or treatment periods b. Documented diagnosis of Type 2 diabetes in stable metformin monotherapy o be on stable metformin monotherapy treatment at a dose at least 1000 mg/day for at least three months at Screening o take metformin as their first and only treatment with anti-diabetes drug therapy (except for short term treatment courses with insulin in connection with hospitalization, etc.) c. Documented diagnosis of Type 2 diabetes in stable treatment with metformin in combination with a sulfonylurea o be on stable metformin and sulfonylurea combination therapy treatment for at least three months at Screening o Metformin dose at least 1000 mg/day at screening o Sulfonylurea dose at least half of the maximally labeled dose for the specific drug o Never have been in more than dual oral treatment for diabetes (except for short term treatment courses with insulin in connection with hospitalization, etc.) d. Documented diagnosis of Type 2 diabetes in stable treatment with metformin, sulfonylurea and thiazolidinedione combination therapy o be on stable metformin and sulfonylurea and thiazolidinedione combination therapy treatment for at least three months at Screening o Metformin dose at least 1000 mg/day at screening o Sulfonylurea dose at least half of the maximally labeled dose for the specific drug o Thiazolidinedione dose at least half of the maximally labeled dose for the specific drug e. Documented diagnosis of Type 2 diabetes in stable treatment with at least two insulin injections (of any type of insulin or insulins) a day with or without metformin o be on stable treatment with at least two injections of insulin with or without metformin for at least three months at Screening o Total daily insulin dose less than 100 U. 3. At the Randomization Visit, patient must still be on the same regimen/dose of antidiabetic medication(s) as at the Screening Visit; does not apply to IGT group. 4. Have an HbA1c between 6.5% and 8%, inclusive, at Screening analyzed by the Central Laboratory; this criterion does not apply to the IGT group 5. Age from 18-74 years, inclusive, and of either sex. |
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E.4 | Principal exclusion criteria |
Exclusion criteria: Patients will be excluded if they fulfill any of the following criteria during screening or prior to randomization: 1. Type 1 diabetes, diabetes that is a result of pancreatic injury or other secondary forms of diabetes, e.g. Cushing s syndrome and acromegaly. 2. Any of the following significant laboratory abnormalities: Serum GAD-antibody positivity analyzed by the Central Laboratory. Clinically significant TSH outside of normal range as judged by the Investigator at Screening analyzed by the Central Laboratory. One retest during the screening period may be allowed per Sponsor approval. Renal function indicating high risk metformin use, including serum creatinine concentrations (≥1.5 mg/dL for males, ≥1.4 mg/dL for females) or other evidence of abnormal creatinine clearance. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN) at Screening, confirmed with repeat measure within one week. Total bilirubin >2 times ULN and/or direct bilirubin greater than the ULN at Screening, confirmed by a repeat measurement within one week. 3. History or current findings of active pulmonary disease (e.g. tuberculosis, fungal diseases) as evidenced by any of the following: History of positive PPD skin test result followed by positive chest x-ray/positive QFT-G test and no completion of treatment. A positive PPD skin test followed by a positive chest x-ray or positive QFT(-G) test (with or without positive chest x-ray) during the screening period. History of a positive QFT(-G) test and no completion of treatment. History of a positive AFB sputum sample and no completion of treatment. Requirement for administration of antibiotics against latent tuberculosis (e.g., isoniazide). Courses of antibiotic therapy started prior to entering the study should not be prematurely terminated to allow inclusion into the study. 4. One of the risk factors for TB such as: History of any of the following: residence in a congregate setting (e.g. jail or prison, homeless shelter, or chronic care facility), substance abuse (e.g. injection or non-injection); health-care workers with unprotected exposure to patients who are at high risk of TB or patients with TB disease before the identification and correct airborne precautions of the patient, or Close contact {i.e. share the same air space in a household or other enclosed environment for a prolonged period (days or weeks, not minutes or hours)} with a person with active pulmonary TB disease. 5. Known presence or suspicion of active or recurrent bacterial, fungal or viral infection at the time of enrollment proven or suspected to be related to immunocompromisation, including patients with evidence of Human Immunodeficiency Virus (HIV) infection. 6. Known presence or suspicion of active or recurrent Hepatitis B and Hepatitis C infections (based on history and/or findings from the Central Lab). 7. Known chronic liver disease of any aetiology. 8. Any surgical or underlying hepatic, hematologic, pulmonary, infectious, autoimmune or gastrointestinal conditions which in the opinion of the investigator immunocompromises the patient and/or places the patient at unacceptable risk for participation in immunodulatory therapy. 9. Any systemic treatment or local treatment of any immune modulating agent in doses with systemic effects. Topical, inhaled or local steroid use, in doses that are not considered to cause systemic effects, are permitted. 10. Live vaccinations within 3 months prior to the Randomization Visit or live vaccinations planned during the trial and up to three months following the last dose. Killed vaccines, including killed Seasonal Influenza and killed H1N1 Influenza vaccines are permitted. 11. PLS SEE PROTOCOL |
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E.5 End points |
E.5.1 | Primary end point(s) |
Evaluate canakinumab effects on change from baseline of meal challenge derived insulin secretion rate relative to glucose 0-2 hours (Φd, at 4 weeks). |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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) | No |
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 | 26 |
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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |