E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 of Study 107 is to obtain CV event data that will be pooled with CV event data from other pivotal Phase 3 studies in a meta-analysis to demonstrate that the upper limit of the 95% confidence interval of the hazard ratio of major adverse cardiac events (MACE) in adult patients on Standard of Care for T2D receiving either ITCA 650 or control, based on the time to first occurrence of any event in the MACE1 CV composite endpoint (CV death, non-fatal myocardial infarction [MI], non-fatal stroke, or hospitalization for unstable angina), does not exceed 1.8.
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E.2.2 | Secondary objectives of the trial |
Other objectives of this trial are to characterize the effects of ITCA 650
on additional specified CV endpoints that will be pooled with CV event
data from other pivotal Phase 3 studies of ITCA 650. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with a diagnosis of T2D
2. Patients with HbA1c ≥6.5% at Screening.
3. High-risk group defined as males and females ≥40 years old with at least one documented occurrence of: CAD, cerebrovascular disease, or symptomatic peripheral arterial disease whose disease, in the Investigator's opinion, is stable, and not in the acute recovery stage of a CV event (i.e., event listed below to have occurred at LEAST 1 month prior to Screening, unless otherwise specified)
4. Low-risk group defined as males and females ≥60 years old with at least one other risk factor in addition to T2D
5. Current treatment with an intermediate-acting and / or long-acting insulin or intermediate and / or long-acting insulin analogue is allowed; if the screening HbA1c value is ≤8.0%, then the total daily dose of intermediate-acting and/or long-acting insulin or intermediate and/or long-acting insulin analogue will be reduced by 20% at randomization
6. Patients who are on a stable treatment regimen of diet and exercise
alone or who are being treated with oral monotherapy or oral
combination antidiabetic therapy with the exception of a
dipeptidylpeptidase-4 (DPP-4) inhibitor or a glucagonlike peptide (GLP)-
1 agonist , or sodium-glucose transporter-2 inhibitor (SGLT2 inhibitor).
7. Women of childbearing potential (WOCBP) must agree to use an adequate method of contraception during the study |
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E.4 | Principal exclusion criteria |
1. Prior treatment with DPP-4 inhibitor or GLP-1 agonist or SGLT2
inhibitors (e.g. canagliflozin) within 3 months prior to Screening
2. Current treatment with rapid-acting insulin or rapid-acting insulin analogues; 3. Requirement of treatment with immunosuppressants or medications that affect gastrointestinal (GI) motility (see Appendix B); 4. Diagnosis of or history of: • Type 1 diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes, e.g., acromegaly and Cushing's Syndrome; • Acute metabolic diabetic complications such as ketoacidosis or hyperosmolar coma within 6 months prior to screening; • Major hypoglycemia (defined as requiring third party assistance) within 1 month prior to Screening. 5. History of acute or chronic pancreatitis; 6. History of thyroidcancer, multiple endocrine neoplasia type 2 (MEN2)
or a family history of medullary thyroid cancer or MEN2
7. Presence of a thyroid nodule detected on physical examination that has not been fully evaluated; 8. Currently scheduled for cardiac surgery or arterial revascularization (carotid, coronary, or peripheral) procedures; 9. Current New York Heart Association (NYHA) Class III or IV heart failure; 10. Diagnosed and/or treated malignancy (except for treated basal or
squamous cell carcinoma of the skin, in situ carcinoma of the cervix, or
in situ prostate cancer) within the past 5 years; 11. Uncontrolled hypertension at Screening defined as a systolic BP >180 mmHg and/or a sitting diastolic BP >100 mmHg (may be repeated after 15 minutes and exclusion based on last measurement). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to first occurrence of any event in the MACE composite endpoint (CV death, non-fatal MI, non-fatal stroke, or hospitalization for unstable angina). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
First occurrence of any event in the MACE composite endpoint |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity: Anti-exenatide antibodies will be measured |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 163 |
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 | No |
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 |
Argentina |
Australia |
Brazil |
Bulgaria |
Canada |
Czech Republic |
Denmark |
Egypt |
Estonia |
Finland |
France |
Germany |
Hungary |
India |
Israel |
Korea, Republic of |
Lithuania |
Malaysia |
Mexico |
Poland |
Romania |
Russian Federation |
Saudi Arabia |
Serbia |
Slovakia |
South Africa |
Spain |
Turkey |
Ukraine |
United Arab Emirates |
United States |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 5 |