Intramuscular Depot Formulation of Aripiprazole as Maintenance Treatment in Patients With Schizophrenia

NCT00705783 | Completed Phase 3 Results DMC

• 1 other identifier: 31-07-246
• Study Type: interventional
• Target: 843
• Locations: 12 countries
• Sites: 110

Brief Summary

The purpose of the trial was to evaluate the efficacy, safety, and tolerability of an intramuscular depot formulation of aripiprazole as maintenance treatment in patients with schizophrenia. The trial was designed into 4 treatment phases. Phase 1 was designed to allow for a patient to be converted from their current antipsychotic treatment to oral non-generic aripiprazole monotherapy (oral conversion phase from 4 to 6 weeks). During Phase 2, the patient was stabilized on oral non-generic aripiprazole monotherapy (oral stabilization phase from a minimum of 4 weeks to a maximum of 12 weeks). Once the patient was stabilized in Phase 2, they entered Phase 3, the single-blind intramuscular (IM) depot aripiprazole stabilization phase. The goal of the phase was to stabilize the patient on the IM depot aripiprazole formulation for a minimum of 12 weeks to a maximum of 36 weeks. When the patient was stabilized, they were eligible to be randomized into the double-blind IM depot maintenance phase (Phase 4). During Phase 4, the patient was assessed for exacerbation of psychotic symptoms and/or impending relapse for up to 52 weeks.

Conditions

Schizophrenia

Keywords

Aripiprazole; Intramuscular (IM) depot; Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Time to Exacerbation of Psychotic Symptoms/Impending Relapse

  A patient experienced an exacerbation of psychotic symptoms/impending relapse if they met any of the following 4 criteria. 1) Clinical Global Impression of Improvement score ≥ 5 and either an increase on any of the following Positive and Negative Syndrome Scale (PANSS) items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content) to a score \> 4 with an increase of ≥ 2 on that item since randomization or an increase on any of the same PANSS items to a score \> 4 and an increase of ≥ 4 on the same combined PANSS items since randomization, 2) Hospitalization due to worsening of psychotic symptoms, 3) Clinical Global Impression of Severity of Suicide (CGI-SS) score of 4 or 5 on Part 1 and/or 6 or 7 on Part 2, or 4) Violent behavior resulting in clinically significant self-injury, injury to another person, or property damage.

  Baseline of the depot maintenance phase to the end of the study (Week 52)

Secondary Outcomes (9)

• Percentage of Patients Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria

  Baseline of the depot maintenance phase to the end of the study (Week 52)

• Percentage of Responders

  Baseline of the depot maintenance phase to the end of the study (Week 52)

• Percentage of Patients Achieving Remission

  Baseline of the depot maintenance phase to the end of the study (Week 52)

• Mean Change From Baseline in the PANSS Total Score

  Baseline of the depot maintenance phase to the end of the study (Week 52)

• Mean Change From Baseline in the Clinical Global Impression - Severity (CGI-S) Score

  Baseline of the depot maintenance phase to the end of the study (Week 52)

Study Arms (2)

Aripiprazole depot

EXPERIMENTAL

Patients received aripiprazole 300 mg or 400 mg depot intramuscularly every 28 days for 52 weeks.

Drug: Aripiprazole depot

Placebo depot

PLACEBO COMPARATOR

Patients received placebo intramuscularly every 28 days for 52 weeks.

Drug: Placebo depot

Interventions

Aripiprazole depot DRUG

Aripiprazole depot was supplied in 400 mg lyophilized vials. Patients received aripiprazole 300 mg if they were unable to tolerate aripiprazole 400 mg.

Also known as: Abilify

Aripiprazole depot

Placebo depot DRUG

Placebo depot was supplied in 400 mg lyophilized vials.

Placebo depot

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects who are able to provide written informed consent and/or consent obtained from a legally acceptable representative (as required by the Institutional Review Board/Institutional Ethics Committee \[IRB/IEC\]), prior to the initiation of any protocol-required procedures.
• Male and female subjects 18 to 60 years of age, inclusive, at time of informed consent.
• Subjects with a current diagnosis of schizophrenia as defined by Diagnostic and Statistical Manual of Mental Disorders, 4th edition text revision (DSM-IV-TR) criteria and a history of the illness for at least 3 years prior to screening.
• Subjects who, in the investigator's judgment, require chronic treatment with an antipsychotic medication.
• Subjects able to understand the nature of the study and follow protocol requirements, including the prescribed dosage regimens, tablet ingestion, IM depot injection, discontinuation of prohibited concomitant medications; who can read and understand the written word in order to complete patient-reported outcomes measures; and who can be reliably rated on assessment scales.

You may not qualify if:

• Subjects with a current DSM-IV-TR diagnosis other than schizophrenia, including schizoaffective disorder, major depressive disorder, bipolar disorder, delirium, dementia, or amnestic or other cognitive disorders. Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.
• Subjects with schizophrenia that are considered resistant/refractory to antipsychotic treatment by history or response only to clozapine.
• Subjects with a significant risk of violent behavior or a significant risk of committing suicide based on history or investigator's judgment.
• Subjects who currently meet DSM-IV-TR criteria for substance dependence, including alcohol and benzodiazepines, but excluding caffeine and nicotine; or 2 positive drug screens for cocaine.
• Subjects who are known to be allergic, intolerant, or unresponsive to prior treatment with aripiprazole or other quinolinones; or hypersensitivity to antipsychotic agents.
• Subjects with uncontrolled thyroid function abnormalities.
• Subjects with a history of seizures, neuroleptic malignant syndrome, clinically significant tardive dyskinesia, or other medical condition that would expose them to undue risk or interfere with study assessments.
• Subjects who are involuntary incarcerated.
• Subjects who have used an investigational agent within 30 days of screening or prior participation in a clinical study with aripiprazole IM depot.
• Subjects with clinically significant abnormalities in laboratory test results, vital signs, or ECG results; and subjects hospitalized for more than 30 days in the 90 days prior to Phase 1.
• Subjects who fail to wash-out from prohibited concomitant medications, including the use of CYP2D6 or CYP3A4 inhibitors or CYP3A4 inducers, antipsychotics, antidepressants (including monoamine oxidase inhibitors \[MAOI}), and mood stabilizers during screening and/or Phase 1.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (110)

Otsuka Investigational Site

Chandler, Arizona, 85226, United States

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Anaheim, California, 92805, United States

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National City, California, 91950, United States

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Oceanside, California, 92056, United States

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San Diego, California, 92123, United States

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Santa Ana, California, 92701, United States

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Highlands Ranch, Colorado, 80130, United States

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Norwalk, Connecticut, 06851, United States

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Altamonte Springs, Florida, 32701, United States

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Bradenton, Florida, 34208, United States

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Hollywood, Florida, 33021, United States

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Maitland, Florida, 32751, United States

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Miami, Florida, 33135, United States

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North Miami, Florida, 33161, United States

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Orange City, Florida, 32763, United States

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Tampa, Florida, 33613, United States

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Atlanta, Georgia, 30328, United States

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Hoffman Estates, Illinois, 60169, United States

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Munster, Indiana, 46321, United States

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Baton Rouge, Louisiana, 70808, United States

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Baton Rouge, Louisiana, 70809, United States

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Lake Charles, Louisiana, 70601, United States

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New Orleans, Louisiana, 70115, United States

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Columbia, Maryland, 21045, United States

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Flowood, Mississippi, 39232, United States

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St Louis, Missouri, 63118, United States

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North Platte, Nebraska, 69101, United States

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Albuquerque, New Mexico, 87131, United States

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Buffalo, New York, 14215, United States

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Cedarhurst, New York, 11516, United States

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Elmsford, New York, 10523, United States

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Holliswood, New York, 11423, United States

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Jamaica, New York, 11418, United States

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Staten Island, New York, 10305, United States

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Cleveland, Ohio, 44109, United States

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Oklahoma City, Oklahoma, 73103, United States

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Philadelphia, Pennsylvania, 19131, United States

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Memphis, Tennessee, 38119, United States

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Austin, Texas, 78754, United States

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DeSoto, Texas, 75115, United States

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Bellevue, Washington, 98007, United States

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Bothell, Washington, 98011, United States

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Richland, Washington, 99354, United States

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Ciudad Autónoma de Bs. As., Buenos Aires, C1058AAJ, Argentina

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La Plata, Buenos Aires, 1900, Argentina

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Lanús Este, Buenos Aires, B1834IBR, Argentina

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Córdoba, Córdoba Province, X5009BIN, Argentina

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Pueyrredón, Córdoba Province, X5004ALB, Argentina

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Mendoza, Mendoza Province, 5500HYF, Argentina

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Mendoza, Mendoza Province, 5500, Argentina

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Rosario, Santa Fe Province, 2000, Argentina

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Buenos Aires, C1405BOA, Argentina

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Buenos Aires, C1425AHQ, Argentina

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Lovech, 5500, Bulgaria

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Pleven, 5800, Bulgaria

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Plovdiv, 4002, Bulgaria

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Radnevo, 6260, Bulgaria

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Region of Veliko Tarnovo, 5047, Bulgaria

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Rousse, 7000, Bulgaria

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Sofia, 1113, Bulgaria

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Varna, 9010, Bulgaria

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Ahmedabad, Gujarat, 380006, India

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Bangalore, Karnataka, 560010, India

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Chennai, Tamil Nadu, 600003, India

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Kanpur, 208005, India

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Mangalore, 575018, India

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Pune, 411004, India

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Tirupati, 517507, India

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Cheras, Kuala Lumpur, 56000, Malaysia

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Kuala Lumpur, Kuala Lumpur, 50603, Malaysia

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Tanjong Rambutan, Perak, 31250, Malaysia

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Kuala Selangor, 43000, Malaysia

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Guadalajara, Jalisco, 44280, Mexico

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Mexico City, Mexico City, 6700, Mexico

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Monterrey, Nuevo León, 64040, Mexico

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San Luis Potosí City, San Luis Potosí, 78218, Mexico

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Culiacán, Sinaloa, 80020, Mexico

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Bataan, Central Luzon, 2105, Philippines

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Mandaluyong, NCR, 1553, Philippines

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Quezon City, NCR, 1104, Philippines

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Iloilo City, Western Visayas, 5000, Philippines

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Cebu City, 6000, Philippines

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Arad, 310022, Romania

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Bucharest, 041914, Romania

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Cluj-Napoca, 400012, Romania

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Craiova, 200620, Romania

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Oradea, 410154, Romania

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Piteşti, 110069, Romania

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Lipetsk, 399083, Russia

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Moscow, 115409, Russia

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Moscow, 115522, Russia

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Moscow, 127473, Russia

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Nizhny Novgorod, 603107, Russia

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Nizhny Novgorod, 603155, Russia

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Saint Petersburg, 188357, Russia

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Saint Petersburg, 190121, Russia

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Saint Petersburg, 192019, Russia

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Smolensk, 214019, Russia

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Belgrade, 11000, Serbia

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Kragujevac, 34000, Serbia

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Košice, 041 90, Slovakia

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Liptovský Mikuláš, 031 23, Slovakia

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Prešov, 081 81, Slovakia

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Rimavská Sobota, 979 12, Slovakia

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Svidník, 089 01, Slovakia

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Changhua, 500, Taiwan

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Hualien City, 981, Taiwan

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Tainan, 704, Taiwan

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Taipei, 110, Taiwan

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Taipei, 112, Taiwan

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Related Publications (3)

• Kane JM, Sanchez R, Perry PP, Jin N, Johnson BR, Forbes RA, McQuade RD, Carson WH, Fleischhacker WW. Aripiprazole intramuscular depot as maintenance treatment in patients with schizophrenia: a 52-week, multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2012 May;73(5):617-24. doi: 10.4088/JCP.11m07530.

  PMID: 22697189 RESULT

• Kane JM, Sanchez R, Baker RA, Eramo A, Peters-Strickland T, Perry PP, Johnson BR, Tsai LF, Carson WH, McQuade RD, Fleischhacker WW. Patient-Centered Outcomes with Aripiprazole Once-Monthly for Maintenance Treatment in Patients with Schizophrenia: Results From Two Multicenter, Randomized, Double-Blind Studies. Clin Schizophr Relat Psychoses. 2015 Summer;9(2):79-87. Epub 2015 Feb 24.

  PMID: 25711509 DERIVED

• Fleischhacker WW, Sanchez R, Johnson B, Jin N, Forbes RA, McQuade R, Baker RA, Carson W, Kane JM. Long-term safety and tolerability of aripiprazole once-monthly in maintenance treatment of patients with schizophrenia. Int Clin Psychopharmacol. 2013 Jul;28(4):171-6. doi: 10.1097/YIC.0b013e3283615dba.

  PMID: 23615694 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

Aripiprazole

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Global Medical Affairs
• Organization: Otsuka Pharmaceutical Development and Commercialization

800 562-3974

Study Officials

• Raymond Sanchez, MD

  Otsuka Pharmaceutical Development & Commercialization, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2008
• First Posted: June 26, 2008
• Study Start: July 1, 2008
• Primary Completion: August 1, 2010
• Study Completion: February 1, 2011
• Last Updated: July 19, 2013
• Results First Posted: July 19, 2013

Record last verified: 2013-06

Locations

ME (5); RO (6); MY (4); TW (5); PH (5); US (43); RU (10); IN (7); BU (8); SE (2); SL (5); AR (10)