FRANCIS-ACS Trial: A Study of the Safety and Efficacy of A 002 in Subjects With Acute Coronary Syndromes

Sponsor

Anthera Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT00743925

Collaborator

(none)

625

Enrollment

Locations

Arms

Duration (Months)

14.2

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The objective of this study is to evaluate the safety and efficacy of A 002 when added to high dose atorvastatin in subjects with an acute coronary syndrome (ACS)

Condition or Disease	Intervention/Treatment	Phase
Acute Coronary Syndrome	Drug: Varespladib Methyl (A-002)	Phase 2

Detailed Description

This is a double-blind randomized parallel group placebo controlled study in subjects presenting with an ACS. Subjects will be randomized to receive either A 002 500 mg once daily (QD) or placebo tablets in addition to 80 mg atorvastatin QD.

Randomization must occur within ≤96 hours of hospital admission for the index ACS event, or, if already hospitalized, within ≤96 hours of index event diagnosis. Follow-up visits will occur at Weeks 2, 4, 8, 12, 16, 20, and 24 post-randomization; and monthly thereafter until study completion.

All enrolled subjects will remain on treatment until all subjects have been treated for a minimum of 24 weeks or until the occurrence of a Major Adverse Cardiac Event (MACE). At that point, all active subjects (those who have not early withdrawn or those that have not already had a MACE) will be brought in for a Final Study Visit. Subjects who complete the Final Study Visit may be eligible to enroll in an open-label extension study for up to 2 years total study drug exposure.

Study Design

Study Type:

Interventional

Actual Enrollment :

625 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

FRANCIS-ACS Trial: A Study of the Safety and Efficacy of A 002 in Subjects With Acute Coronary Syndromes

Study Start Date :

Jul 1, 2008

Actual Primary Completion Date :

Jan 1, 2010

Actual Study Completion Date :

Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 A-002 (500 mg QD) plus Atorvastatin (80 mg QD)	Drug: Varespladib Methyl (A-002) 2 Tablets (250 mg each) once daily for at least 24 weeks in combination with Atorvastatin (80 mg tablet once a day). Other Names: A-002 Varespladib Lipitor Atorvastatin
Placebo Comparator: 2 Matching Placebo tablets plus Atorvastatin (80 mg QD)	Drug: Varespladib Methyl (A-002) 2 Tablets (250 mg each) once daily for at least 24 weeks in combination with Atorvastatin (80 mg tablet once a day). Other Names: A-002 Varespladib Lipitor Atorvastatin

Arm

Intervention/Treatment

Active Comparator: 1

A-002 (500 mg QD) plus Atorvastatin (80 mg QD)

Drug: Varespladib Methyl (A-002)

2 Tablets (250 mg each) once daily for at least 24 weeks in combination with Atorvastatin (80 mg tablet once a day).

Other Names:

A-002

Varespladib

Lipitor

Atorvastatin

Placebo Comparator: 2

Matching Placebo tablets plus Atorvastatin (80 mg QD)

Drug: Varespladib Methyl (A-002)

2 Tablets (250 mg each) once daily for at least 24 weeks in combination with Atorvastatin (80 mg tablet once a day).

Other Names:

A-002

Varespladib

Lipitor

Atorvastatin

Outcome Measures

Primary Outcome Measures

Mean percent changes in LDL hs-CRP, sPLA2 and other biomarkers will be compared between the 2 treatment groups. [8 Weeks]

Secondary Outcome Measures

The occurrence of MACEs will be examined for any treatment-related trends at study completion. [End of Study]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men and women ≥18 years of age
A diagnosis of unstable angina, NSTEMI, or STEMI
Any one of the following criteria: Diabetes, CRP ≥2 mg/L, or metabolic syndrome
Subjects must be randomized within 96 hours of the index event
Percutaneous revascularization, if required or planned, must occur prior to randomization

Exclusion Criteria:

Subjects must NOT meet any of the following exclusion criteria:
Subjects enrolled in another experimental (interventional) protocol within the past 30 days prior to Screening.
Subjects treated for cancer within the previous 5 years except for skin basal cell carcinoma or carcinoma in situ of the cervix, with measures other than a minor, complete surgical excision (e.g., chemotherapy), or radiation therapy.
The presence of severe liver disease with cirrhosis, recent active hepatitis, active chronic hepatitis, ALT or AST >3 x ULN, biliary obstruction with hyperbilirubinemia (total bilirubin >2 x ULN)
Active cholecystitis, gall bladder symptoms, or potential hepato-biliary abnormalities
The presence of severe renal impairment (CrCl <30 mL/min or creatinine >3 x ULN), nephrotic syndrome, or patients undergoing dialysis
Uncontrolled diabetes mellitus (HbA1c >11% within the last 1 month prior to Screening)
Females who are nursing, pregnant, or intend to become pregnant during the time of the study, or females of child-bearing potential who have a positive pregnancy test during screening evaluation. Women of child-bearing potential must also use a reliable method of birth control during the study and for 1 month following completion of therapy. A reliable method for this study is defined as one of the following: oral or injectable contraceptives, IUD, contraceptive implants, tubal ligation, hysterectomy, a barrier method (diaphragm with spermicidal foam or jelly, or a condom).
Subjects who have a history of alcohol or drug abuse within 1 year of study entry
Subjects living too far from participating center or unable to return for follow-up visits
Subjects who in the opinion of the Investigator are a poor medical or psychiatric risk for therapy with an investigational drug, are unreliable, or have an incomplete understanding of the study which may affect their ability to take drugs as prescribed or comply with instructions
Known HIV, Hepatitis B or C virus, or tuberculosis infection
Acute bacterial, fungal or viral infection
Any current statin therapy at maximum recommended dosage. For atorvastatin, fluvastatin, lovastatin, pravastatin and simvastatin 80 mg QD at the time of the index event and for rosuvastatin 20 mg QD to 40 mg QD
Drugs that are potent inhibitors of cytochrome P450 unless they can be withdrawn
Subjects with NYHA Class III or IV heart failure, or LVEF <30
Subjects with moderate or severe aortic stenosis, aortic regurgitation, mitral stenosis or mitral regurgitation
Ventricular arrhythmias requiring chronic drug treatment or ICD
Subjects with no stenosis or stenosis <50% on angiography
Subjects with a pacemaker or persistent LBBB
LDL-C >200 mg/dL (5.2 mmol/L)
Fasting triglyceride levels of ≥400 mg/dL (4.5 mmol/L)

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Cardiological hospital of The Patriarchate of all Georgia	Tbilisi	Georgia	0102
2	Tbilisi State Medical University, Al. Aladashvili University Clinic	Tbilisi	Georgia	0102
3	Cardio Reanimation Centre	Tbilisi	Georgia	0141
4	Cardiological Clinic "Guli"	Tbilisi	Georgia	0144
5	Tbilisi LTD Cardiology Clinic	Tbilisi	Georgia	0144
6	Emergency Cardiology Center by acad. G. Chapidze	Tbilisi	Georgia	0159
7	National Center of Therapy	Tbilisi	Georgia	0159
8	Multiprofile Clinical Hospital of Tbilisi #2	Tbilisi	Georgia	0164
9	Diagnostic Services Clinic	Tbilisi	Georgia	0179
10	Limited Company "ADAPTI" The Clinic of Angiocardiology "ADAPTI"	Tbilisi	Georgia	0186
11	New Hospital Medical Union	Ekaterinburg	Russian Federation	620109
12	Municipal Healthcare Institution	Gatchina	Russian Federation	188300
13	Municipal Healthcare Institution	Kemerovo	Russian Federation	650002
14	Non-State Healthcare Institution	Kemerovo	Russian Federation	650055
15	Krasnoyarsk Medical Academy	Krasnoyarsk	Russian Federation	660022
16	State Healthcare Intstitution of Moscow	Moscow	Russian Federation	111539
17	City Clinical Hospital №12	Nizhniy Novgorod	Russian Federation	603003
18	Municipal Healthcare Institution	Novosibirsk	Russian Federation	630008
19	Regional State Healthcare Institution	Novosibirsk	Russian Federation	630047
20	Municipal Healthcare Institution	Perm	Russian Federation	614107
21	St.Petersburg State Healthcare Institution	Saint-Petersburg	Russian Federation	190000
22	St.Petersburg State Healthcare Institution	Saint-Petersburg	Russian Federation	191144
23	Saint-Petersburg State Healthcare Institution	Saint-Petersburg	Russian Federation	198205
24	St.Petersburg State Healthcare Institution	Saint-Petersburg	Russian Federation	199106
25	State Healthcare Institution	Samara	Russian Federation	443070
26	Saratov State Medical University	Saratov	Russian Federation	410012
27	Federal State Institution	Saratov	Russian Federation	410028
28	State Healthcare Institution	St-Petersburg	Russian Federation	195197
29	St.Petersburg State Healthcare Institution	St-Petersburg	Russian Federation	195257
30	State Educational Institution for Further Professional Training	St.Petersburg	Russian Federation	191015
31	Federal State Healthcare Institution	St.Petersburg	Russian Federation	194044
32	State Institution Research Cardiology Institute	Tomsk	Russian Federation	634012
33	Tyumen Cardiology Center,	Tyumen	Russian Federation	625026
34	Municipal Clinical Hospital No. 27	Kharkiv	Ukraine	61002
35	Department of Cardiology of Central Clinical Hospital	Kharkiv	Ukraine	61018
36	L.T. Malaya Institute of Therapy of AMS of Ukraine	Kharkiv	Ukraine	61039
37	Kharkiv Medical Academy of Post-Graduate Education	Kharkiv	Ukraine	61178
38	Kyiv City Clinical Hospital #1	Kyiv	Ukraine	02175
39	National Scientific Center	Kyiv	Ukraine	03680
40	Lviv Danylo Halytsky National University	Lviv	Ukraine	79000
41	Lviv Regional State Clinical Treatment and Diagnostics Cardiology Center	Lviv	Ukraine	79015
42	Uzhgorod National University	Uzhgorod	Ukraine	88014
43	Zaporizhzhya Regional Cardiological Dispensary	Zaporizhzhya	Ukraine	69000
44	Zhytomyr city hospital #1	Zhytomyr	Ukraine	10002