Efficacy and Safety of Ramelteon Sublingual in Adult Patients With Acute Depressive Episodes Associated With Bipolar I Disorder

NCT ID: NCT01467700

Last Updated: 2016-05-16

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

490 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-12-31

Study Completion Date

2015-03-31

Brief Summary

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The purpose of this study is to determine the efficacy and safety of Ramelteon, once daily (QD), sublingual (SL), in adult participants with acute depressive episodes associated with Bipolar I disorder.

Detailed Description

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Ramelteon sublingual formulation is being developed by Takeda Pharmaceutical Company Limited for maintenance therapy of Bipolar I disorder.

Participants will be seen twice during the first week of treatment, weekly during the first 2 weeks of treatment and then every 2 weeks up to the end of the 8-week treatment period. Participants who complete the 8-week treatment period will have a follow-up visit approximately seven days after the last visit. A safety follow-up phone call will be made 30 days after completion of the 8-week treatment period.

Based on the recommendation of the Independent Data Monitoring Committee which determined that the study data had met pre-determined criteria for futility, Takeda has made a decision to terminate the study. No safety concerns were identified by the Independent Data Monitoring Committee

Conditions

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Acute Depressive Episode

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Ramelteon SL 0.1 mg

Ramelteon SL 0.1 mg, tablets, sublingual (SL) \[dissolved under the tongue\], once daily (QD), every night at bedtime for up to 8 weeks.

Group Type EXPERIMENTAL

Ramelteon SL

Intervention Type DRUG

Ramelteon SL tablets

Ramelteon SL 0.4 mg

Ramelteon SL 0.4 mg, tablets, sublingual, once daily, every night at bedtime for up to 8 weeks.

Group Type EXPERIMENTAL

Ramelteon SL

Intervention Type DRUG

Ramelteon SL tablets

Ramelteon SL 0.8 mg

Ramelteon SL 0.8 mg tablets, sublingual, once daily, every night at bedtime for up to 8 weeks.

Group Type EXPERIMENTAL

Ramelteon SL

Intervention Type DRUG

Ramelteon SL tablets

Placebo

Ramelteon SL placebo-matching, tablets, sublingual, once daily, every night at bedtime for up to 8 weeks.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Ramelteon placebo-matching tablets

Interventions

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Ramelteon SL

Ramelteon SL tablets

Intervention Type DRUG

Placebo

Ramelteon placebo-matching tablets

Intervention Type DRUG

Other Intervention Names

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TAK-375SL

Eligibility Criteria

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Inclusion Criteria

1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
3. The participant is a man or woman aged between 18 and 75 years, inclusive.
4. The participant suffers from Bipolar I Disorder, Most Recent Episode Depressed as the primary diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria (classification code 296.5x) and confirmed by the Structured Clinical Interview for DSM Disorders (SCID).
5. The reported duration of the current Major Depressive Episode (MDE) is at least four weeks and less than 6 months.
6. The participant has a Young Mania Rating Scale (YMRS) score of ≤10 both at the Screening and Baseline visits.
7. The participant has a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥24 at the Screening and Baseline Visits.
8. The participant has a Clinical Global Impression Scale - Severity (CGI-S) score of ≥4 at the Screening and Baseline Visits.
9. Hamilton Rating Scale for Anxiety (HAM-A) score is ≤21 at Screening and Baseline visits.
10. The participant has a lithium and/or valproate levels within therapeutic range (0.6 - 1.2 mEq/L for lithium or 50-125 mcg/ml for valproate) at screening. If the patient does not have a lithium and/or valproate level within therapeutic range at screening, they must have a lithium and/or valproate levels within the therapeutic range between Day - 15 to Day -30 of screening.
11. A female participant of childbearing potential who is sexually active and agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and for 30 days after the last dose.
12. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent through the duration of the study and for 30 days after the last dose.

Exclusion Criteria

1. The participant has received any investigational compound \<30 days before Screening or 5 half-lives prior to Screening.
2. The participant has received ramelteon in a previous clinical study or has ever used ramelteon.
3. The participant is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress.
4. The participant has one or more of the following:

* Any current psychiatric disorder other than Bipolar I Disorder, Most Recent Episode Depressed as defined in the DSM-IV-TR, as assessed by the SCID.
* Current or history of: schizophrenia, unipolar depression with psychotic features, bipolar depression with psychotic features, any other psychotic disorder (with the exception of psychosis associated with a manic episode), mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV-TR.
* Current diagnosis or history of alcohol or other substance abuse or dependence (excluding nicotine or caffeine) as defined in the DSM-IV-TR that has not been in full and sustained remission for at least one year from the day of screening. (Participant must also have negative urine drug screen prior to Baseline).
* Presence or history of a clinically significant neurological disorder (including epilepsy).
* Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease, etc).
* Any Axis II disorder that might compromise the study.
* History of Rapid Cycling Bipolar Disorder: Patients who have more than 8 episodes of mood disorder per year.
5. The participant experienced the first episode of mood disorder after the age of 65 years.
6. The current depressive symptoms of the participant are considered by the investigator to have been resistant to 2 adequate treatment trials with any of the mood stabilizers (specifically started to treat the current depressive episode) and/or antidepressant medications of at least 6 weeks duration each.
7. The participant is on any other psychotropic medications except for lithium (serum levels 0.8 to mEq/L) or valproate (serum levels 50 to 125 mcg/ml) at the Screening visit.
8. The participant is on lithium and/or valproate for less than 30 days prior to screening.
9. If the participant is on antidepressant medications and/or antipsychotic medications (used as a mood stabilizer) and the patient is considered appropriate by the PI, these medications must be washed out for at least 2 weeks prior to the Screening visit.
10. The participant has received electroconvulsive therapy, vagal nerve stimulation, or repetitive transcranial magnetic stimulation within 6 months prior to Screening.
11. The participant has started receiving formal cognitive or behavioral therapy, systematic psychotherapy within 30 days prior to screening or plans to initiate such therapy during the study.
12. The participant has a significant risk of suicide according to the investigator's clinical judgment or has a score ≥ 5 on item 10 (suicidal thoughts) of the MADRS or has made a suicide attempt in the previous 6 months.
13. The participant has taken or is anticipated that the participant will take at least 1 of the disallowed concomitant medications.
14. The participant has a clinically significant unstable illness, for example hepatic impairment or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, hematological, infectious, dermatological disorder or metabolic disturbance as determined by Investigator.
15. The participant has a history or current diagnosis of Fibromyalgia, Chronic Fatigue Syndrome, Chronic Pain Syndrome or Sleep apnea.
16. The participant has a previous history of cancer that had been in remission for less than 5 years prior to the first dose of study medication. This criterion does not include those participants with basal cell or stage I squamous cell carcinoma of the skin.
17. The participant has 1 or more laboratory value outside the normal range, based on the blood or urine samples taken at the Screening Visit, that are considered by the investigator to be clinically significant; or the participant has any of the following values at the Screening Visit:

* A serum creatinine value \>1.5 times the upper limits of normal (xULN).
* A serum total bilirubin value \>1.5 xULN.
* A serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value \>2 xULN.
18. The participant has glycosylated hemoglobin (HbA1C) ≥7% at baseline and no prior diagnosis of diabetes and/or treatment for diabetes. NOTE: Participants with known diabetes are not excluded.
19. The participant has a thyroid stimulating hormone (TSH) value outside the normal range at the Screening Visit that is deemed clinically significant by the investigator. If TSH is outside the normal range, a free T4 will be obtained.
20. The participant has clinically significant abnormal vital signs as determined by the investigator.
21. The participant has an abnormal electrocardiogram (ECG) as determined by the central reader and confirmed as clinically significant by the investigator.
22. The participant has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy.
23. The participant, in the opinion of the investigator, is unlikely to comply with the clinical study protocol or is unsuitable for any reason.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Takeda

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

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Birmingham, Alabama, United States

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Dothan, Alabama, United States

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Muscle Shoals, Alabama, United States

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Phoenix, Arizona, United States

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Fayetteville, Arkansas, United States

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Little Rock, Arkansas, United States

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Bellflower, California, United States

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Costa Mesa, California, United States

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Garden Grove, California, United States

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Harbor City, California, United States

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Huntington Park, California, United States

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Irvine, California, United States

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Lomita, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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Murrieta, California, United States

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National City, California, United States

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Oceanside, California, United States

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Orange, California, United States

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Paramount, California, United States

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Rancho Cucamonga, California, United States

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Redondo Beach, California, United States

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Riverside, California, United States

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Sacramento, California, United States

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San Diego, California, United States

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San Jose, California, United States

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San Ramon, California, United States

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Sherman Oaks, California, United States

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Torrance, California, United States

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Wildomar, California, United States

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Colorado Springs, Colorado, United States

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Denver, Colorado, United States

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Norwalk, Connecticut, United States

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Washington D.C., District of Columbia, United States

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Clearwater, Florida, United States

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Coral Gables, Florida, United States

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Coral Springs, Florida, United States

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Edgewater, Florida, United States

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Hialeah, Florida, United States

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Jacksonville, Florida, United States

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Leesburg, Florida, United States

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Miami, Florida, United States

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Miami Beach, Florida, United States

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Miami Lakes, Florida, United States

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Orange City, Florida, United States

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Orlando, Florida, United States

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Pembroke Pines, Florida, United States

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Plantation, Florida, United States

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Port Charlotte, Florida, United States

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Saint Cloud, Florida, United States

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Tampa, Florida, United States

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Vero Beach, Florida, United States

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Atlanta, Georgia, United States

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Dunwoody, Georgia, United States

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East Point, Georgia, United States

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Smyrna, Georgia, United States

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Suwanee, Georgia, United States

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Honolulu, Hawaii, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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Gurnee, Illinois, United States

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Hoffman Estates, Illinois, United States

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Libertyville, Illinois, United States

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Skokie, Illinois, United States

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Brownsburg, Indiana, United States

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Manhattan, Kansas, United States

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Topeka, Kansas, United States

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Wichita, Kansas, United States

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Elizabethtown, Kentucky, United States

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Lexington, Kentucky, United States

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Paducah, Kentucky, United States

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Mandeville, Louisiana, United States

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Metairie, Louisiana, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Fall River, Massachusetts, United States

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Bloomfield Hills, Michigan, United States

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Detroit, Michigan, United States

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Kalamazoo, Michigan, United States

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Flowood, Mississippi, United States

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Hazelwood, Missouri, United States

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Saint Charles, Missouri, United States

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St Louis, Missouri, United States

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Washington, Missouri, United States

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Lincoln, Nebraska, United States

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Las Vegas, Nevada, United States

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Cherry Hill, New Jersey, United States

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Albuquerque, New Mexico, United States

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Brooklyn, New York, United States

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Cedarhurst, New York, United States

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Fresh Meadows, New York, United States

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New York, New York, United States

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Rochester, New York, United States

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Staten Island, New York, United States

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Charlotte, North Carolina, United States

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Columbiana, North Carolina, United States

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Durham, North Carolina, United States

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Greensboro, North Carolina, United States

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Raleigh, North Carolina, United States

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Salisbury, North Carolina, United States

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Wilmington, North Carolina, United States

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Fargo, North Dakota, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Dayton, Ohio, United States

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Franklin, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Portland, Oregon, United States

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Allentown, Pennsylvania, United States

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Duncansville, Pennsylvania, United States

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Harleysville, Pennsylvania, United States

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McMurray, Pennsylvania, United States

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Media, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Lincoln, Rhode Island, United States

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Columbia, South Carolina, United States

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Greer, South Carolina, United States

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Old Point Station, South Carolina, United States

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Clarksville, Tennessee, United States

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Knoxville, Tennessee, United States

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Memphis, Tennessee, United States

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Austin, Texas, United States

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Bellaire, Texas, United States

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Corpus Christi, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Irving, Texas, United States

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Nassau Bay, Texas, United States

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Plano, Texas, United States

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San Antonio, Texas, United States

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Bountiful, Utah, United States

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Newport News, Virginia, United States

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Norfolk, Virginia, United States

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Richmond, Virginia, United States

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Virginia Beach, Virginia, United States

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Kirkland, Washington, United States

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Richland, Washington, United States

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Seattle, Washington, United States

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Clarksburg, West Virginia, United States

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Milwaukee, Wisconsin, United States

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Buenos Aires, , Argentina

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Córdoba, , Argentina

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Mendoza, , Argentina

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Santa Fe, , Argentina

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Antofagasta, , Chile

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Arauco, , Chile

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Elqui, , Chile

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Santiago, , Chile

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Bello, Antioquia, Colombia

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Antioquia, , Colombia

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Barranquilla, , Colombia

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Bogotá, , Colombia

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Mexicali, Estado de Baja California, Mexico

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León, Guanajuato, Mexico

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Mexico City, Mexico City, Mexico

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Monterrey, Nuevo León, Mexico

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San Lucas, Tepetlacalco, Mexico

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Mérida, Yucatán, Mexico

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México, , Mexico

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San Luis Potosí City, , Mexico

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Countries

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United States Argentina Chile Colombia Mexico

Related Links

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Other Identifiers

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U1111-1122-7380

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-375SL_201

Identifier Type: -

Identifier Source: org_study_id

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