Phase 2 N=526 Randomized Quadruple-blind Treatment

A Study to Evaluate the Safety of 12 Weeks of Dosing With GW856553 and Its Effects on Inflammatory Markers, Infarct Size, and Cardiac Function in Subjects With Myocardial Infarction Without ST-segment Elevation

Acute Coronary Syndrome

Bottom Line

View on ClinicalTrials.gov: NCT00910962 ↗

Enrolled (actual)

526

Serious AEs

24.0%

Results posted

Oct 2017

Primary outcome: Primary: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) — 97; 138; 131; 269 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: GW856553 (Drug); Placebo (Drug)
Age: Adult, Older Adult · 45+ yrs
Sex: All
Sponsor: GlaxoSmithKline
Primary completion: Mar 2012

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)	97; 138; 131; 269; 32; 51	—
PRIMARY Number of Participants With Any Major Adverse Cardiovascular Events (MACE)	23; 28; 34; 62	0.4110
PRIMARY Number of Participants With Any Pure MACE	19; 21; 29; 50	0.2990
PRIMARY Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline	2; 7; 11; 18; 14; 20	—
PRIMARY Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline	1; 4; 2; 6; 0; 0	—
PRIMARY Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline	4; 7; 4; 11; 1; 4	—
PRIMARY Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Any Time Post-Baseline	34; 41; 40; 81; 77; 115	—
PRIMARY Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline	0; 0; 2; 2; 1; 1	—
PRIMARY Mean High-sensitive C-Reactive Protein (hsCRP) Value at Week 12	1.52; 1.30; 1.46; 1.38	0.151
PRIMARY Mean Cardiac Troponin I (cTnI) Area Under Concentration-time Curve (AUC) Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First)	1.7; 1.1; 1.3; 1.2	0.83
SECONDARY Mean hsCRP Over Hospitalization Period and Through Week 14	4.03; 4.26; 4.31; 4.29; 9.10; 6.76	0.040 sig
SECONDARY Mean Interleukin-6 (IL-6) Value at 24 Hours Post-randomization and at Weeks 2 and 12	10.59; 6.08; 7.11; 6.57; 3.50; 2.75	<0.001 sig
SECONDARY Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First)	11.5; 10.5; 9.8; 10.2; 9.0; 7.8	0.66
SECONDARY Peak cTnI Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First)	4.02; 3.49; 3.54; 3.52	0.92
SECONDARY Mean Brain Natriuretic Peptide (BNP) at Discharge and Week 12	72.56; 65.84; 73.24; 69.49; 49.41; 37.41	0.57
SECONDARY Mean Infarct Size Prior to Discharge From Hospital (Approximately Day 3) and at Week 12	7.804; 5.575; 5.848; 5.697; 5.620; 4.783	0.254
SECONDARY Mean Percent Left Ventricular Ejection Fraction (LVEF) at Week 12	56.615; 59.571; 59.738; 59.658	0.124
SECONDARY Mean Left Ventricular End-diastolic Volume (LVEDV) and Left Ventricular End-systolic Volume (LVESV) at Week 12	132.895; 125.942; 130.642; 128.386; 58.660; 52.115	0.025 sig
SECONDARY Mean Left Ventricular Mass at Week 12	145.463; 141.449; 154.194; 148.076	0.109
SECONDARY Mean Regional Wall Motion Score Index at Week 12	0.306; 0.179; 0.186; 0.182	0.023 sig
SECONDARY Mean Hyperenhancement Score Index at Week 12	0.350; 0.282; 0.249; 0.265	0.137

Summary

This is a randomized, double-blind, placebo-controlled, parallel group, multi-center study to evaluate initial safety and efficacy of GW856553 in subjects with NSTEMI. Up to approximately 525 subjects will be randomized to meet the MRI recruitment target (90 subjects in substudy.) All subjects will continue to receive the local standard of care for the duration of the study.

Eligibility Criteria

Inclusion Criteria

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.
Subject able to be randomized within 18 hours of presentation.
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 the study].
Male or female subject who is 45 years of age or older.
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) greater than 40 MlU/ml and estradiol less than 40 pg/ml (less than 140 pmol/L) is confirmatory), or child-bearing potential and agrees to use one of the contraception methods listed in the protocol for the duration of dosing and until the first follow-up visit (approximately 2 weeks post last-dose).
Negative urine or serum pregnancy test (in women of child-bearing potential only).
Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until the first follow-up visit (approximately 2 weeks post last-dose).
QTcB or QTcF greater than 530 msec.
Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria

History of severe heart failure defined as NYHA class III or IV or those with known severe LV dysfunction [ejection fraction less than 30%] regardless of symptomatic status.
Suspected aortic dissection.
Severe aortic stenosis or other severe valvular disease.
Current known life-threatening condition other than vascular disease (e.g. severe chronic airways disease) that may prevent a subject from completing the study.
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, 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.
History of myopathy or rhabdomyolysis.
Current or chronic history of liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Known to be Hepatitis B or Hepatitis C positive.
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.
Current or anticipated use of BCRP substrates with a narrow therapeutic index (e.g. daunorubicin, doxorubicin, topotecan, mitoxantrone).
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..
Known alcohol or drug abuse within the past 6 months.
Previous exposure to GW856553.
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.
Any other subject whom the Investigator deems unsuitable for the study (e.g., due to either medical reasons, laboratory abnormalities, expected study medication non-comp

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Data sourced from ClinicalTrials.gov (NCT00910962). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.