Adult Bipolar Mania

This study has been completed.
Sponsor:
Collaborator:
Quintiles
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00931723
First received: June 29, 2009
Last updated: March 27, 2012
Last verified: March 2012
  Purpose

The purpose of this study is to determine if lithium 600-1800 mg/day is effective when added to quetiapine fumarate extended release (quetiapine XR or SEROQUEL® XR) 400-800 mg/day in treating acute mania and if so, how it compares with placebo (a non-active capsule, like a sugar pill, that looks like lithium).


Condition Intervention Phase
Acute Mania
Drug: Quetiapine fumarate XR
Drug: Lithium
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An International, Multicenter, Double-blind, Randomized, Placebo-controlled, Phase IV Study of the Safety and Efficacy of Lithium Versus Placebo as an Add on to SEROQUEL XR (Quetiapine Fumarate) in Adult Patients With Acute Mania

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to Final Assessment (Day 43) [ Time Frame: Change in YMRS total score from baseline to Day 43. ] [ Designated as safety issue: No ]
    The YMRS total score ranges from 0 to 60 where higher scores indicate more severe mania, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in manic symptoms. Total score ≤12 indicates remission (13-19=minimal symptoms; 20-25=mild mania, 26-37=moderate mania, 38-60=severe mania).


Secondary Outcome Measures:
  • The Number of Patients With Clinically Significant Response. [ Time Frame: 43 days (from baseline to Day 43) ] [ Designated as safety issue: No ]
    The number of patients with clinically significant response (defined as ≥50% reduction from baseline to Day 43 in the YMRS total score) was calculated. The YMRS total score ranges from 0 to 60 where higher scores indicate more severe mania, thus, a negative change (or 50% reduction) from baseline indicates a reduction (or improvement) in manic symptoms.

  • Remission [ Time Frame: Days 8 to 43 ] [ Designated as safety issue: No ]

    The number of patients with clinically significant remission (defined as YMRS total score ≤12) from Days 8 to 43) was calculated.

    The Young Mania Rating Scale total score ranges from 0 to 60 where higher scores indicate more severe mania, thus, a negative change (or 50% reduction) from baseline indicates a reduction (or improvement) in manic symptoms. Total score ≤12 indicates remission (13-19=minimal symptoms; 20-25=mild mania, 26-37=moderate mania, 38-60=severe mania).


  • Change From Baseline to Day 43 in CGI-BP-S (Clinical Global Impressions for Bipolar Disorder-Severity of Illness) [ Time Frame: Change from baseline to Day 43. ] [ Designated as safety issue: No ]
    The CGI-BP-S scale rates the severity of the patient's illness at the time of assessment and is scored from 1 to 7 (1=normal, not ill to 7=very severely ill). Higher CGI-BP-S scores indicate greater illness severity.

  • Change From Baseline to Day 43 in CGI-BP-C (Clinical Global Impressions for Bipolar Disorder-Change From Preceding Phase) [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]
    The CGI-BP-C scale rates how much the patient's illness has improved or worsened compared to the phase immediately preceding treatment and is scored on a scale from 1 to 8 (1=very much improved to 7=very much worse; 8=not applicable). A missing score will be used when a scale scored as 8 (not applicable). CGI-BP-C scores >4 indicate worsening, while scores <4 indicate improvement.

  • Improvement of Overall Bipolar Illness [ Time Frame: Day 43. ] [ Designated as safety issue: No ]

    The number of patients with a CGI-BP-C of "Much" or "Very much" improved in overall bipolar illness assessment at Day 43 was calculated.

    The CGI-BP-C scale rates how much the patient's illness has improved or worsened compared to the phase immediately preceding treatment and is scored on a scale from 1 to 8 (1=very much improved to 7=very much worse; 8=not applicable). A missing score will be used when a scale scored as 8 (not applicable). CGI-BP-C scores >4 indicate worsening, while scores <4 indicate improvement.


  • Change From Baseline to Day 43 in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Change from baseline to Day 43. ] [ Designated as safety issue: No ]
    The MADRS is a 10-item scale that evaluates depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. Higher MADRS scores indicate higher levels of depressive symptoms.

  • Change From Baseline to Day 43 in Positive and Negative Syndrome Scale (PANSS) Total Score [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]
    The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia and are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score is the sum of all 30 individual-item scores and ranges from 30 to 210.A negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

  • Change From Baseline to Day 43 in PANSS Activation Subscale Score [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]
    The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia and are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS activation subscale score for effect on agitation and aggression is the sum of 6 PANSS individual items (ie, hostility, poor impulse control, excitement, uncooperativeness, poor rapport and tension) and ranges from 6 to 42. A negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

  • Change From Baseline to Day 43 in PANSS Positive Subscale Score [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]
    The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia and are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS positive subscale score is the sum of the 7 positive item scores (ie, delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution and hostility) and ranges from 7 to 49. A negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

  • Change From Baseline to Day 43 in Each YMRS Item Score No. 1 [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]
    The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4 (0=normal). This analysis is for Item 1 (Elevated mood) which ranges from 0 to 4 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

  • Change From Baseline to Day 43 in Each YMRS Item Score No. 2 [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]
    The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4 (0=normal). This analysis is for Item 2 (increased motor activity-energy) which ranges from 0 to 4 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

  • Change From Baseline to Day 43 in Each YMRS Item Score No. 3 [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]
    The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4 (0=normal). This analysis is for Item 3 (sexual interest) which ranges from 0 to 4 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

  • Change From Baseline to Day 43 in Each YMRS Item Score No. 4 [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]
    The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4 (0=normal). This analysis is for Item 4 (sleep) which ranges from 0 to 4 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

  • Change From Baseline to Day 43 in Each YMRS Item Score No. 5 [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]
    The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4 (0=normal). This analysis is for Item 5 (Irritability) which ranges from 0 to 8 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

  • Change From Baseline to Day 43 in Each YMRS Item Score No. 6 [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]
    The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4 (0=normal). This analysis is for Item 6 (speech-rate and amount) which ranges from 0 to 8 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

  • Change From Baseline to Day 43 in Each YMRS Item Score No. 7 [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]
    The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4. This analysis is for Item 7 (language-thought disorder) which ranges from 0 to 4 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

  • Change From Baseline to Day 43 in Each YMRS Item Score No. 8 [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]
    The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4. This analysis is for Item 8 (content) which ranges from 0 to 8 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

  • Change From Baseline to Day 43 in Each YMRS Item Score No. 9 [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]
    The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4. . This analysis is for Item 9 (disruptive-aggressive behavior) which ranges from 0 to 8 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

  • Change From Baseline to Day 43 in Each YMRS Item Score No. 10 [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]
    The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4. This analysis is for Item 10 (appearance) which ranges from 0 to 4 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

  • Change From Baseline to Day 43 in Each YMRS Item Score No. 11 [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]
    The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4. This analysis is for Item 11 (insight) which ranges from 0 to 4 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.


Enrollment: 356
Study Start Date: June 2009
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Seroquel XR and Lithium
Drug: Quetiapine fumarate XR
Oral treatment, once daily, Day 1 = 300 mg, Day 2 and thereafter 600 mg. Dose might be adjusted as from Day 3 by the discretion of the investigator.
Other Name: Seroquel XR
Drug: Lithium
Oral treatment, twice daily, Days 1 and 2 = 600 mg/day, Days 3-8 = 900 mg/day. Dose adjustment from day 9 to end of study will be at the discretion of the investigator.
Placebo Comparator: 2
Seroquel XR and placebo
Drug: Quetiapine fumarate XR
Oral treatment, once daily, Day 1 = 300 mg, Day 2 and thereafter 600 mg. Dose might be adjusted as from Day 3 by the discretion of the investigator.
Other Name: Seroquel XR
Drug: Placebo
Oral treatment twice daily.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provision of informed consent before any study procedures are performed.
  • The patient must have a documented clinical diagnosis for bipolar I disorder, including recent episode manic or mixed, and being male of females age 18-65 years, inclusive.
  • Patients may be outpatients or inpatients at enrollment visit, but all patients must be inpatients when randomized and remain inpatients until discharged at the discretion of the investigator.

Exclusion Criteria:

  • The patient can not have had up to 8 mood episodes during the past 12 months and not been continuously hospitalized for acute bipolar for up to 3 weeks immediately before participating in the study.
  • The patient can not have a past diagnosis of stroke or medically documented transient ischemic attacks (TIA) or a history of seizure disorder, except for febrile convulsions.
  • The patient must not have received electroconvulsive treatment (ECT) within 90 days before participating in the study and in the doctors judgement pose a current suicidal or homicidal risk.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00931723

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Locations
Belgium
Research Site
Cedex, Belgium
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Dendermonde, Belgium
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Montignies-sur-sambre, Belgium
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Overpelt, Belgium
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Tournai, Belgium
Bulgaria
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Burgas, Bulgaria
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Cedex, Bulgaria
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Kazanlak, Bulgaria
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Pazardjik, Bulgaria
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Plovdiv, Bulgaria
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Radnevo, Bulgaria
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Sofia, Bulgaria
Germany
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Berlin, BE, Germany
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Koln, NW, Germany
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Berlin, Germany
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Cedex, Germany
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Mannheim, Germany
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Munchen, Germany
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Nurnberg, Germany
India
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Visakhapatnam, Andh Prad, India
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Ahmedabad, Gujarat, India
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Bangalore, Karna, India
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Mangalore, Karna, India
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Manipal, Karna, India
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Nashik, Mahara, India
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Jaipur, Rajasthan, India
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Kanpur, Uttar Prad, India
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Cedex, India
Israel
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Bat Yam, Israel
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Beer Ya'acov, Israel
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Cedex, Israel
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Haifa, Israel
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Petach-tikva, Israel
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Tel-hashomer, Israel
Poland
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Bydgoszcz, Poland
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Cedex, Poland
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Choroszcz, Poland
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Gorlice, Poland
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Katowice, Poland
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Krakow, Poland
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Lublin, Poland
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Poznan, Poland
Russian Federation
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Arkhangelsk, Russian Federation
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Cedex, Russian Federation
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Chita, Russian Federation
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Kazan, Russian Federation
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Moscow, Russian Federation
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Saratov, Russian Federation
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St Petersburg, Russian Federation
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St. Petersburg, Russian Federation
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Voronezh, Russian Federation
South Africa
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Bloemfontein, Free State, South Africa
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Vereeniging, Free State, South Africa
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Worcester, W Cape, South Africa
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Cape Town, South Africa
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Cedex, South Africa
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Johannesburg, South Africa
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Port Elizabeth, South Africa
Ukraine
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Cedex, Ukraine
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Dnipropetrovsk, Ukraine
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Donetsk, Ukraine
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Kharkov, Ukraine
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Kiev, Ukraine
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Odessa, Ukraine
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Vinnitsia, Ukraine
Sponsors and Collaborators
AstraZeneca
Quintiles
Investigators
Study Director: Michael Castiglione AstraZeneca
Principal Investigator: Michel Bourin, Professeur Neurobiologie de l'anxiété et de la dépression Faculté de Médecine
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00931723     History of Changes
Other Study ID Numbers: D144AC00003
Study First Received: June 29, 2009
Results First Received: November 17, 2011
Last Updated: March 27, 2012
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Bulgaria: Bulgarian Drug Agency
Germany: Federal Institute for Drugs and Medical Devices
India: Drugs Controller General of India
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: FSI Scientific Center of Expertise of Medical Application
Russia: Ministry of Health of the Russian Federation
South Africa: Medicines Control Council
Ukraine: State Pharmacological Center - Ministry of Health

Keywords provided by AstraZeneca:
Acute Mania
Mania, Adults
Seroquel
Acute Mania in Adult Patients

Additional relevant MeSH terms:
Bipolar Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Lithium
Quetiapine
Lithium Carbonate
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Antimanic Agents
Antidepressive Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014