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Efficacy and Safety of Elagolix in Combination With Estradiol/Norethindrone Acetate for the Management of Heavy Menstrual Bleeding Associated With Uterine Fibroids in Premenopausal Women (Replicate Study)

Phase 3
Completed
Conditions
Heavy Menstrual Bleeding
Uterine Fibroids
Interventions
Registration Number
NCT02691494
Lead Sponsor
AbbVie
Brief Summary

This study seeks to evaluate the efficacy, safety and tolerability of elagolix alone and in combination with estradiol/norethindrone acetate for the management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
378
Inclusion Criteria
  • Subject is a premenopausal female at the time of Screening.
  • Subject has a diagnosis of uterine fibroids documented by a pelvic ultrasound (transabdominal ultrasound/transvaginal ultrasound).
  • Subject has heavy menstrual bleeding associated with uterine fibroids as evidenced by menstrual blood loss > 80 mL during each of two screening menses as measured by the alkaline hematin method.
  • Subject has negative urine and/or serum pregnancy test in Screening and just prior to first dose.
  • Subject has an adequate endometrial biopsy performed during Screening, the results of which show no clinically significant endometrial pathology.
Exclusion Criteria
  • Subject has screening pelvic ultrasound or saline infusion sonohysterography results that show a clinically significant gynecological disorder.
  • Subject has history of osteoporosis or other metabolic bone disease.
  • Subject has clinically significant abnormalities in clinical chemistry, hematology, or urinalysis.
  • Subject has a history of major depression or post-traumatic stress disorder (PTSD) within 2 years of screening, OR a history of other major psychiatric disorder at any time (e.g., schizophrenia, bipolar disorder).
  • Subject is using any systemic corticosteroids for over 14 days within 3 months prior to Screening or is likely to require treatment with systemic corticosteroids during the course of the study. Over the counter and prescription topical, inhaled, intranasal or injectable (for occasional use) corticosteroids are allowed.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo for ElagolixPlacebo for both elagolix twice daily (BID) and norethindrone acetate (E2/ NETA) once daily (QD)
PlaceboPlacebo for Estradiol/Norethindrone AcetatePlacebo for both elagolix twice daily (BID) and norethindrone acetate (E2/ NETA) once daily (QD)
ElagolixPlacebo for Estradiol/Norethindrone AcetateElagolix 300 mg BID and placebo for E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD
Elagolix + E2/NETAEstradiol/Norethindrone AcetateElagolix 300 mg BID and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD
ElagolixElagolixElagolix 300 mg BID and placebo for E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD
Elagolix + E2/NETAElagolixElagolix 300 mg BID and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD
Primary Outcome Measures
NameTimeMethod
Percentage of Participants Meeting the Criteria for ResponderFinal Month (the last 28 days prior to and including the Reference Day), up to Month 6

Percentage of responders, defined as participants who met the following conditions:

* Menstrual blood loss (MBL) volume \< 80 mL during the Final Month (the last 28 days prior to and including the Reference Day, which is defined as the last visit date during the Treatment Period (last treatment visit date) or the last dose date if there are evaluable alkaline hematin data after the last treatment visit date and prior to or on the last dose date), and

* ≥ 50% reduction in MBL volume from Baseline to the Final Month.

Participants who prematurely discontinued study drug due to "lack of efficacy," "requires surgery or invasive intervention for treatment of uterine fibroids," or "adverse events" were considered non-responders regardless of whether she meets the two aforementioned responder criteria or not.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in MBL Volume to Month 3Month 0 (Baseline), Month 3

Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL.

Percentage of Participants With Baseline Hemoglobin <= 10.5 g/dL Who Have an Increase in Hemoglobin > 2 g/dL at Month 6Month 0 (Baseline), Month 6
Change From Baseline in MBL Volume to Month 1Month 0 (Baseline), Month 1

Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL.

Change From Baseline in MBL Volume to the Final MonthBaseline and Final Month (the last 28 days prior to and including the Reference Day), up to Month 6

Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL.

The Reference Day is defined as the last visit date during the Treatment Period (last treatment visit date) or the last dose date if there are evaluable alkaline hematin data after the last treatment visit date and prior to or on the last dose date.

Percentage of Participants With Suppression of Bleeding at the Final MonthFinal Month (the last 28 days prior to and including the Reference Day), up to Month 6

Suppression of bleeding is defined as having 0 days of bleeding (spotting is allowed) during the Final Month with the interval starting from Study Day 11.

The Reference Day is defined as the last visit date during the Treatment Period (last treatment visit date) or the last dose date if there are evaluable alkaline hematin data after the last treatment visit date and prior to or on the last dose date.

Change From Baseline in MBL Volume to Month 6Month 0 (Baseline), Month 6

Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL.

Trial Locations

Locations (105)

University of California, Los Angeles /ID# 149760

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Los Angeles, California, United States

Mount Vernon Clinical Res, LLC /ID# 144297

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Atlanta, Georgia, United States

Clinical Trial Investigators /ID# 152470

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Tustin, California, United States

Ideal Clinical Research Inc. /ID# 149757

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Aventura, Florida, United States

Unified Women's Clinical Research-Greensboro /ID# 149588

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Greensboro, North Carolina, United States

Baltimore Suburban Health /ID# 154638

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Baltimore, Maryland, United States

Invictus Clinical Research Group,LLC /ID# 141859

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Miami, Florida, United States

The Woman's Hospital of Texas /ID# 144319

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Houston, Texas, United States

BI Research Center /ID# 149143

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Houston, Texas, United States

Accent Clinical Trials /ID# 149753

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Las Vegas, Nevada, United States

The Christ Hospital /ID# 150104

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Cincinnati, Ohio, United States

HCP Clinical Research LLC /ID# 154434

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Huntington Beach, California, United States

KO Clinical Research, LLC /ID# 144299

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Fort Lauderdale, Florida, United States

Precision Research Org, LLC /ID# 144335

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Miami Lakes, Florida, United States

Mobile, Ob-Gyn, P.C. /ID# 144294

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Mobile, Alabama, United States

Atlanta Women's Research Inst /ID# 144303

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Atlanta, Georgia, United States

Willowbend Health and Wellness /ID# 144318

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Plano, Texas, United States

Wake Research Associates, LLC /ID# 144307

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Raleigh, North Carolina, United States

Centex Studies, Inc. - Houston /ID# 150106

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Houston, Texas, United States

Center of Reproductive Medicin /ID# 167235

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Webster, Texas, United States

Access Clinical Trials, Inc. /ID# 167333

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Nashville, Tennessee, United States

Alabama Clinical Therapeutics, LLC /ID# 152258

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Birmingham, Alabama, United States

Choice Research, LLC /ID# 150988

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Dothan, Alabama, United States

Brown, Pearson, Guepet Gynecology /ID# 151020

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Fairhope, Alabama, United States

Visions Clinical Research-Tucs /ID# 151017

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Tucson, Arizona, United States

Mesa Obstetricians and Gynecol /ID# 149139

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Mesa, Arizona, United States

Diagnamics Inc. /ID# 152469

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Encinitas, California, United States

Core Healthcare Group /ID# 151016

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Cerritos, California, United States

Alliance Research Centers /ID# 149752

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Laguna Hills, California, United States

Farid Yasharpour MD Medical Co /ID# 149770

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San Fernando, California, United States

Bayview Research Group LLC /ID# 153799

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Valley Village, California, United States

Futura Research, Inc. /ID# 149759

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Norwalk, California, United States

Seffner Premier Health Care, P /ID# 167480

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Brandon, Florida, United States

Emerson Clinical Research Inst /ID# 152348

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Washington, District of Columbia, United States

Olympian Clinical Research /ID# 149756

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Clearwater, Florida, United States

Solutions Through Adv Rch /ID# 151021

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Jacksonville, Florida, United States

All Wmns HC of West Broward /ID# 144298

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Plantation, Florida, United States

Meridien Research /ID# 167100

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Kenneth City, Florida, United States

Physician Care Clin. Res., LLC /ID# 149766

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Sarasota, Florida, United States

Paramount Research Solutions /ID# 149291

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Alpharetta, Georgia, United States

Suncoast Clinical Research /ID# 149765

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New Port Richey, Florida, United States

Martin Health System Center /ID# 152263

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Stuart, Florida, United States

Oncova Clinical Research, Inc. /ID# 149764

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Saint Cloud, Florida, United States

Qps-Mra, Llc /Id# 144325

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South Miami, Florida, United States

Gyn-Care, Inc. /ID# 149341

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Smyrna, Georgia, United States

Agile Clinical Research Trials /ID# 167074

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Atlanta, Georgia, United States

Meridian Clinical Research, LLC /ID# 149144

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Savannah, Georgia, United States

Axcess Medical Research /ID# 149769

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Wellington, Florida, United States

Atlanta Gynecology Research Institute /ID# 151014

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Suwanee, Georgia, United States

Virtus Research Consultant,LLC /ID# 144296

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Wellington, Florida, United States

Masters of Clinical Research, Inc. /ID# 167400

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Augusta, Georgia, United States

Georgia Regents University /ID# 144295

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Augusta, Georgia, United States

Womens Healthcare Assoc, DBA /ID# 149762

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Idaho Falls, Idaho, United States

University of Chicago /ID# 152257

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Chicago, Illinois, United States

Advanced Clinical Research /ID# 149767

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Meridian, Idaho, United States

Affinity Clinical Research /ID# 167119

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Oak Brook, Illinois, United States

Center for Women's Research, Inc /ID# 144300

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Palos Heights, Illinois, United States

The Iowa Clinic /ID# 150105

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West Des Moines, Iowa, United States

Women's Health Advantage /ID# 144301

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Fort Wayne, Indiana, United States

Clinical Trials Management, LLC - Covington /ID# 144314

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Covington, Louisiana, United States

PRN Professional Research Network of Kansas, LLC /ID# 152265

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Wichita, Kansas, United States

NECCR Fall River LLC /ID# 149584

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Fall River, Massachusetts, United States

Womens Health Center /ID# 154209

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Glen Burnie, Maryland, United States

Maryland Ctr for Sexual Health /ID# 149778

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Lutherville, Maryland, United States

Saginaw Valley Med Res Group /ID# 149768

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Saginaw, Michigan, United States

Jersey Shore University Medical Center /ID# 149779

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Neptune, New Jersey, United States

SUNY Downstate Medical Center /ID# 144311

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Brooklyn, New York, United States

Manhattan Medical Research /ID# 167077

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New York, New York, United States

Weill Cornell Medicine /ID# 149585

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New York, New York, United States

Duplicate_Unified Women's Clinical Research-Fayetteville /ID# 149587

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Fayetteville, North Carolina, United States

Eastern Carolina Women's Centr /ID# 144309

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New Bern, North Carolina, United States

Clinical Inquest Center Ltd /ID# 148728

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Beavercreek, Ohio, United States

CTI Clinical Research Center /ID# 149761

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Cincinnati, Ohio, United States

Alpha Research Associates LLC /ID# 152471

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Dayton, Ohio, United States

Comprehensive Womens Care /ID# 144306

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Westerville, Ohio, United States

Family Medical Associates /ID# 145668

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Levittown, Pennsylvania, United States

University of Pennsylvania /ID# 149586

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Philadelphia, Pennsylvania, United States

Clinical Research of Philadelphia, LLC /ID# 151015

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Philadelphia, Pennsylvania, United States

Chattanooga Women for Women /ID# 167051

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Hixson, Tennessee, United States

Holston Medical Group /ID# 149763

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Bristol, Tennessee, United States

The Womens Physician Group /ID# 144317

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Memphis, Tennessee, United States

Reading Hosp Clncl Trials Ofc /ID# 149583

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West Reading, Pennsylvania, United States

The Jackson Clinic, PA /ID# 145670

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Jackson, Tennessee, United States

Chattanooga Medical Research /ID# 145667

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Chattanooga, Tennessee, United States

Inquest Clinical Research /ID# 149755

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Baytown, Texas, United States

Texas Health Presbyterian Hosp /ID# 149142

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Dallas, Texas, United States

Baylor College of Medicine /ID# 149141

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Houston, Texas, United States

FMC Science /ID# 151802

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Lampasas, Texas, United States

Southampton Women's Health /ID# 152325

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Franklin, Virginia, United States

Clinical Trials of Texas,Inc. /ID# 144322

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San Antonio, Texas, United States

Tidewater Physicians for Women /ID# 144321

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Norfolk, Virginia, United States

Zain Research /ID# 151018

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Richland, Washington, United States

Medicor Research Inc. /ID# 153406

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Sudbury, Ontario, Canada

Victory Reproductive Care /ID# 150247

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Windsor, Ontario, Canada

Virginia Mason Medical Center /ID# 149758

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Seattle, Washington, United States

University of South Florida /ID# 149754

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Tampa, Florida, United States

Lotus Gynecology /ID# 149140

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Austin, Texas, United States

University of Florida /ID# 149751

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Gainesville, Florida, United States

Bluegrass Clinical Research /ID# 150103

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Louisville, Kentucky, United States

Montefiore Medical Center /ID# 149582

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Bronx, New York, United States

Women Under Study, LLC /ID# 144312

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New Orleans, Louisiana, United States

Clinical Research Partners, LLC /ID# 144310

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Richmond, Virginia, United States

Alliance Womens Health /ID# 152468

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Richmond, Virginia, United States

Rowan University SOM /ID# 152697

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Stratford, New Jersey, United States

Pinewest Ob-Gyn, Inc. /ID# 145671

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High Point, North Carolina, United States

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