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 (Solstice)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00910962
First received: May 28, 2009
Last updated: March 13, 2014
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Acute Coronary Syndrome
Drug: GW856553
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • A safety evaluation will be made by assessment of all adverse events, major adverse cardiovascular events as defined in the protocol, safety laboratory tests (including liver function values), vital signs and 12-lead ECG parameters [ Time Frame: 14 weeks ] [ Designated as safety issue: Yes ]
  • The change in hsCRP at Week 12 compared with baseline [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • cTnI AUC over 72 hours post-randomization or until hospital discharge (whichever comes first) [ Time Frame: 72 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The change in hsCRP over hospitalization period and through Week 14 [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
  • IL-6 at 24 hours post-randomization and at Weeks 2 and 12 [ Time Frame: 24 hours, 2 weeks, and 12 weeks ] [ Designated as safety issue: No ]
  • CK-MB AUC over 72 hours post-randomization or until hospital discharge (whichever comes first) [ Time Frame: approximately 72 hours ] [ Designated as safety issue: No ]
  • [SUB-STUDY] Infarct size, as measured by delayed contrast-enhanced MRI prior to discharge from hospital (~Day 3) and at Week 12 [ Time Frame: approximately 72 hours and at 12 weeks ] [ Designated as safety issue: No ]
  • [SUB-STUDY] Cardiac functional measures via MRI at Week 12 including left ventricular dimensions, left ventricular ejection fraction and regional wall motion score (visual estimate) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 540
Study Start Date: October 2009
Study Completion Date: April 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment A
7.5 mg GW856553 starting dose, followed 12 hours later by 7.5mg twice daily for 12 weeks
Drug: GW856553
7.5 mg GW856553 starting dose, followed 12 hours later by 7.5mg BID
Experimental: Treatment B
15 mg GW856553 starting dose, followed 12 hours later by 7.5mg twice daily for 12 weeks
Drug: GW856553
15 mg GW856553 starting dose, followed 12 hours later by 7.5mg BID
Placebo Comparator: Treatment C
Placebo twice daily for 12 weeks
Drug: Placebo
Placebo

  Eligibility

Ages Eligible for Study:   45 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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-compliance).
  • Unwillingness or inability to follow the procedures outlined in the protocol.
  • Previous MI or coronary artery bypass graft (CABG) surgery.
  • History of kidney transplant or a history of contrast nephropathy.
  • Contraindication to MRI scanning (as assessed by local MRI safety questionnaire) which includes but is not limited to: intracranial aneurysm clips or other metallic objects; history of intra-orbital metal fragments that have not been removed by an MD; pacemakers and non-MR compatible heart valves; inner ear implants; history of claustrophobia in MR.
  • Allergy to MRI contrast enhancement agent (gadolinium).
  • Estimated creatinine clearance by Cockcroft-Gault formula < 30 mL/min.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00910962

  Show 109 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00910962     History of Changes
Other Study ID Numbers: 111810
Study First Received: May 28, 2009
Last Updated: March 13, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
India: Ministry of Health
Netherlands: Ministry of Health, Welfare and Sports
Poland: Ministry of Health
Spain: Ministry of Health
Canada: Health Canada
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
United States: Food and Drug Administration
Australia: Therapeutic Goods Administration

Keywords provided by GlaxoSmithKline:
NSTEMI, acute coronary syndrome, p38 MAPK inhibitor, GW856553, percutaneous coronary intervention

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Acute Coronary Syndrome
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Angina Pectoris
Chest Pain
Pain
Signs and Symptoms

ClinicalTrials.gov processed this record on April 17, 2014