E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with myocardial infarction without ST-segment elevation |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064347 |
E.1.2 | Term | Non ST segment elevation myocardial infarction |
E.1.2 | System Organ Class | 10007541 - Cardiac 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 |
1. To assess the safety of GW856553 in subjects with NSTEMI. 2. To assess the effects of GW856553 on biomarkers of inflammation in subjects with NSTEMI over the 12 weeks of treatment. 3. To assess the effects of GW856553 on infarct size and cardiac function during the peri-infarct period and during the ensuing 12 weeks of treatment.
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E.2.2 | Secondary objectives of the trial |
Various exploratory endpoints, including coronary pressure/flow, PK/PD and quality of life will be evaluated.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
There are two sub-studies; Cardian MRI Substudy and Coronary Flow and pressure Sub-study. These are described within the main protocol for PM1111810 and therefore do not have a separate date and version number. The purpose of the MRI Substudy is to determine myocardial infarct size by delayed enhancement MRI. The rationale for the Coronary Flow and pressure sub-study is that coronary flow reserve and fractional flow reserve are strong predictors of coronary event rates. |
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E.3 | Principal inclusion criteria |
1. Subjects with a NSTEMI, defined as: • symptoms (e.g. chest pain, dyspnea) consistent with acute coronary syndrome, lasting at least 10 minutes, with most recent symptoms occurring within the 24 hours prior to presentation, • without persistent ST-segment elevation on admission 12-lead ECG, and • with Troponin (T or I) above the upper limit of normal (ULN) for the local institution within 18 hours of presentation. 2. Subject able to be randomized within 18 hours of presentation. 3. Subjects to be managed with an early invasive strategy, with PCI likely to occur at least 2 hours after the start of dosing [subjects who do not undergo PCI will not be withdrawn from study]. 4. Male or female subject who is 45 years of age or older. 5. A female subject is eligible to participate if she is of: • Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory), or • Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1.1 of the protocol for the duration of dosing and until the first follow-up visit (~2 weeks post last-dose). 6. Negative urine or serum pregnancy test (in women of child-bearing potential only). 7. Male subjects must agree to use one of the contraception methods listed in Section 8.1.2 of the protocol. This criterion must be followed from the time of the first dose of study medication until the first follow-up visit (~2 weeks post last-dose). 8. QTcB or QTcF </= 530 msec. 9. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
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E.4 | Principal exclusion criteria |
1. History of severe heart failure defined as NYHA class III or IV or those with known severe LV dysfunction [ejection fraction (EF) < 30%] regardless of symptomatic status. 2. Suspected aortic dissection. 3. Severe aortic stenosis or other severe valvular disease. 4. Current known life-threatening condition other than vascular disease (e.g. severe chronic airways disease) that may prevent a subject from completing the study. 5. Subjects with rheumatoid arthritis, connective tissue disorders and other conditions known to be associated with active chronic or acute inflammation (e.g. inflammatory bowel disease, osteomyelitis, pneumonia, sepsis etc.). Intermittent conditions treated with short-term oral antibiotics (e.g. typical URI), or conditions that are not currently exacerbated (e.g. gout with no current flair) may be included. 6. History of myopathy or rhabdomyolysis. 7. Current or chronic history of liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 8. Known to be Hepatitis B or Hepatitis C positive. 9. Current or anticipated use of systemic steroids (oral or IV). Inhaled, intranasal and topical steroids are allowed. A single prophylactic dose of systemic steroid is allowed at time of PCI for subjects with contrast allergy. 10. Current or anticipated use of BCRP substrates with a narrow therapeutic index (e.g. daunorubicin, doxorubicin, topotecan, mitoxantrone); see Section 9.2. 11. Previously diagnosed cancer that has not been in complete remission for at least 5 years. Localized carcinomas of the skin and carcinoma in situ of the cervix that have been resected or ablated for cure are not exclusionary. 12. Known alcohol or drug abuse within the past 6 months. 13. Previous exposure to GW856553. 14. Use of another investigational product within 30 days or 5 half-lives (whichever is the longer) preceding the first dose of IP in the current study. 15. Any other subject whom the Investigator deems unsuitable for the study (e.g., due to either medical reasons, laboratory abnormalities, expected study medication noncompliance). 16. Unwillingness or inability to follow the procedures outlined in the protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety Endpoints • A safety evaluation will be made by assessment of all adverse events, major adverse cardiovascular events (MACE) as defined in Section 11.3, safety laboratory tests (including liver function values), vital signs and 12-lead ECG parameter
Inflammatory Endpoints •hsCRP at Week 12
Myocardial Infarct Sizeand Cardiac Function Endpoints •cTnI AUC over 72 hours post-randomization or until hospital discharge (whichever comes first).
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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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As stated in Section 9.4 of the protocol;
There will be no treatment with GW856553 after the end of the study. Subjects enrolled into this study will already be receiving the appropriate standard of care, and this care will be continued at the end of the study (as per the subject's local physician). |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |