Study to Evaluate the Efficacy and Safety of Hydrocodone Bitartrate Extended-Release Tablets (CEP-33237) for Relief of Moderate to Severe Pain in Patients With Osteoarthritis or Low Back Pain Who Require Opioid Treatment for an Extended Period of Time

Phase 3

Completed

Conditions: Chronic Pain

Interventions: Drug: Hydrocodone ER
Drug: Placebo

Registration Number: NCT01240863

Lead Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Brief Summary: The primary objective of this study is to evaluate efficacy of hydrocodone extended-release (ER) tablets compared with placebo in alleviating moderate to severe pain in patients with osteoarthritis or low back pain as assessed by the weekly Average Pain Intensity (API) at week 12.

Detailed Description: The study consisted of a screening period of approximately 7 to 14 days, an open label titration period of up to 6 weeks, and a double blind treatment period of 12 weeks.

Participants entered the open label titration period and received hydrocodone ER tablets beginning with 15 mg every 12 hours for 3 to 7 days. The objective of the open label titration period was to find the successful dose of hydrocodone ER tablets that produced stable pain relief (defined as an Average Pain Intensity (API) score of 4 or less on the 11-point numerical rating scale for either 3 consecutive days or 3 out of 5 consecutive days while the patient was maintained on the same dose of study drug for up to 7 days). Patients returned to the study center prior to each dose adjustment.

Participants who met the criterion of a stabilized dose were randomly assigned into the 12 week, double blind, placebo controlled treatment period on the final day of the open label titration period (baseline visit). Patients began treatment with double blind study drug at the effective dose of hydrocodone ER tablets achieved during the titration period or matching placebo. Rescue medication was permitted in addition to the study drug during the double blind treatment period.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 391

Inclusion Criteria

The patient is able to speak English and is willing to provide written informed consent, including a written opioid agreement, to participate in this study.
The patient must be willing and able to successfully self-administer the study drug, comply with study restrictions, complete the electronic diary, and return to the clinic for scheduled study visits as specified in this protocol.
Women of childbearing potential (not surgically sterile or 2 years postmenopausal), must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study, and have a negative pregnancy test at screening.
The patient has pain of at least 3 months' duration associated with osteoarthritis or low back pain.
The patient reports an average pain intensity score, over the prior 24 hours, of 5 or more on the 11-point numerical rating scale.
If the patient is receiving physical therapy, biofeedback therapy, acupuncture therapy, or herbal remedies, these therapies must remain unchanged during the study.
The patient must not participate in other study involving an investigational agent while enrolled into the present study.

Exclusion Criteria

The patient has known or suspected hypersensitivities, allergies, or other contraindications to any ingredient in the study drug.
The patient has a recent history (within 5 years) or current evidence of alcohol or other substance abuse with the exception of nicotine or caffeine.
The patient has medical or psychiatric disease that, in the opinion of the investigator, would compromise collected data.
The patient is taking a total (ie, around-the-clock plus rescue medication) of more than 135 mg/day of oxycodone, or equivalent, during the 14 days prior to screening.
The patient has a history of suicidality.
The patient is expected to have surgery during the study.
The patient's primary painful condition under study is related to any source of chronic pain other than osteoarthritis or low back pain.
The patient is pregnant or lactating.
The patient has active malignancy.
The patient has human immunodeficiency virus (HIV).
In the judgment of the investigator, the patient has any clinically significant deviation from normal in the physical examination and/or clinical laboratory test values.
The patient has cardiopulmonary disease that would, in the opinion of the investigator, significantly increase the risk of treatment with opioids.
The patient has participated in a study involving an investigational drug in the previous 30 days.
The patient has received a monoamine oxidase inhibitor (MAOI) within 14 days before the first treatment with study drug.
The patient has any other medical condition or is receiving concomitant medication/therapy (e.g., regional nerve block) that would, in the opinion of the investigator, compromise the patient's safety or compliance with the study protocol, or compromise collected data.
The patient is involved in active litigation in regard to the pain currently being treated.
The patient has a positive urine drug screen (UDS) that is not medically explainable.
The investigator feels that the patient is not suitable for the study for any reason.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Hydrocodone ER	Participants were administered hydrocodone ER tablets at dosages of 15, 30, 45, 60, or 90 mg every 12 hours at the dosage deemed successful for managing their pain during the titration period. During the treatment period, participants were administered placebo tablets every 12 hours that matched the dosage deemed successful for managing their pain during the titration period. A step-wise, double-blind schedule to tamper off active drug was implemented during the first 2 weeks of the 12-week, double-blind, placebo-controlled treatment period to reduce the risk of withdrawal effects in participants randomly assigned to placebo.
Hydrocodone ER	Hydrocodone ER	Participants were administered hydrocodone ER tablets at dosages of 15, 30, 45, 60, or 90 mg every 12 hours at the dosage deemed successful for managing their pain during the titration period. During the 12-week, double-blind, placebo-controlled treatment period, participants randomly assigned to hydrocodone ER were administered tablets every 12 hours at the dosage deemed successful for managing their pain during the titration period.
Placebo	Placebo	Participants were administered hydrocodone ER tablets at dosages of 15, 30, 45, 60, or 90 mg every 12 hours at the dosage deemed successful for managing their pain during the titration period. During the treatment period, participants were administered placebo tablets every 12 hours that matched the dosage deemed successful for managing their pain during the titration period. A step-wise, double-blind schedule to tamper off active drug was implemented during the first 2 weeks of the 12-week, double-blind, placebo-controlled treatment period to reduce the risk of withdrawal effects in participants randomly assigned to placebo.

Primary Outcome Measures

Name	Time	Method
Change From Baseline to Week 12 in Weekly Average Pain Intensity (wAPI)	Baseline (end of Open-Label Titration Period), Week 12 of Double-blind Treatment Period	The primary efficacy variable was the change from baseline to week 12 in the wAPI. The API over the previous 24 hours, based on the 11-point Numerical Rating Scale (NRS 11), was collected daily by e-diary. The Week 12 wAPI scores from the previous 7 days were calculated for each study visit and averaged. The baseline wAPI score was calculated by averaging API scores from 3 to 12 days when the successful dose of hydrocodone extended release was confirmed at the end of the open label titration period, before patients were randomly assigned study drug. In the case of missing week-12 data due to early withdrawal from the study, or excessive rescue medication usage, the wAPI for week 12 was imputed. The Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain on a Likert-type scale in which 0 is no pain and 10 is the worst pain imaginable. Negative change from baseline values indicate lessening in pain intensity.

Secondary Outcome Measures

Name	Time	Method
Clinician Assessment of Patient Function (CAPF) at Week 8	Week 8 of the Double-blind Treatment Period	Clinicians assessed participants across 5 dimensions: * Patients general activities * Patients walking ability * Patients ability to work/perform activities of daily living * Patients relationships with others * Patients enjoyment of life Assessments are rated on a 7-point scale, in which 1 is very much worsened and 7 is very much improved since the start of the study.
Participants With a Weekly Average Pain Intensity (wAPI) Increase From Baseline Exceeding 33%	Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period	The API over the previous 24 hours, based on the 11-point Numerical Rating Scale (NRS 11), was collected daily by e-diary. The wAPI scores from the previous 7 days were calculated for each study visit and averaged. The baseline wAPI score was calculated by averaging API scores from 3 to 12 days when the successful dose of hydrocodone extended release was confirmed at the end of the open label titration period, before patients were randomly assigned study drug. The Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain on a Likert-type scale in which 0 is no pain and 10 is the worst pain imaginable.
Participants With a Weekly Average Pain Intensity (wAPI) Increase From Baseline Exceeding 50%	Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period	The API over the previous 24 hours, based on the 11-point Numerical Rating Scale (NRS 11), was collected daily by e-diary. The wAPI scores from the previous 7 days were calculated for each study visit and averaged. The baseline wAPI score was calculated by averaging API scores from 3 to 12 days when the successful dose of hydrocodone extended release was confirmed at the end of the open label titration period, before patients were randomly assigned study drug. The Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain on a Likert-type scale in which 0 is no pain and 10 is the worst pain imaginable.
Weekly Average Pain Intensity (wAPI) Scores During the Double-blind Treatment Period	Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period	The API over the previous 24 hours, based on the 11-point Numerical Rating Scale (NRS 11), was collected daily by e-diary. The wAPI scores from the previous 7 days were calculated for each study visit and averaged. The baseline wAPI score was calculated by averaging API scores from 3 to 12 days when the successful dose of hydrocodone extended release was confirmed at the end of the open label titration period, before patients were randomly assigned study drug. The Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain on a Likert-type scale in which 0 is no pain and 10 is the worst pain imaginable.
Weekly Average Worst Pain Intensity (WPI) Scores During the Double-blind Treatment Period	Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period	The WPI was recorded by the patient in the e-diary daily throughout the study, based on the Numeric Rating Scale (NRS-11). Participants were asked to select the number that best described their WPI over the previous 24 hours. Values were averaged for each week. The Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain on a Likert-type scale in which 0 is no pain and 10 is the worst pain imaginable.
Clinician Assessment of Patient Function (CAPF) at Week 4	Week 4 of the Double-blind Treatment Period	Clinicians assessed participants across 5 dimensions: * Patients general activities * Patients walking ability * Patients ability to work/perform activities of daily living * Patients relationships with others * Patients enjoyment of life Assessments are rated on a 7-point scale, in which 1 is very much worsened and 7 is very much improved since the start of the study.
Clinician Assessment of Patient Function (CAPF) at Week 12	Week 12 of the Double-blind Treatment Period	Clinicians assessed participants across 5 dimensions: * Patients general activities * Patients walking ability * Patients ability to work/perform activities of daily living * Patients relationships with others * Patients enjoyment of life Assessments are rated on a 7-point scale, in which 1 is very much worsened and 7 is very much improved since the start of the study.
Clinician Assessment of Patient Function (CAPF) at Endpoint	Endpoint of the Double-blind Treatment Period (up to week 12)	Clinicians assessed participants across 5 dimensions: * Patients general activities * Patients walking ability * Patients ability to work/perform activities of daily living * Patients relationships with others * Patients enjoyment of life Assessments are rated on a 7-point scale, in which 1 is very much worsened and 7 is very much improved since the start of the study. Endpoint values are the last observed postbaseline data.
Patient Assessment of Function (PAF) at Week 4	Week 4 of the Double-blind Treatment Period	The PAF is a self-administered questionnaire used to measure patients' assessment of their own ability to function in normal activities. Answers to the 7 questions were rated on a 7 point scale in which 1 was very much worsened and 7 were very much improved since the start of the study. The seven functional areas are: * ability to go to work * ability to perform at work (includes both work outside the home and housework) * ability to walk * ability to exercise * ability to participate in social events * ability to have sex * ability to enjoy life
Percentage of Participants Withdrawn From the Study During the Double-Blind Treatment Period By Reason	Day 1 to Week 12 of the double-blind treatment period	Percentage of participants who withdrew from the study during the double-blind treatment period. Withdrawal is due to any cause, including lack of efficacy.
Kaplan-Meier Estimates for Time to Discontinuation From the Study	Day 1 to Week 12 of the double-blind treatment period	Kaplan-Meier estimates for time to discontinuation from the study (due to any cause) was calculated as the number of days since participants were randomly assigned to study drug treatment, ie, the difference between the date the participants withdrew and the date participants were randomly assigned to study drug treatment. The censoring flag was set to 0 if a participant was withdrawn from study drug treatment early and was set to 1 if the participant completed the 12 week treatment period. Censoring time was calculated as the difference of treatment completion date (ie, date of last study drug administration) and date participant was randomly assigned to study drug treatment.
Patient Assessment of Function (PAF) at Week 8	Week 8 of the Double-blind Treatment Period	The PAF is a self-administered questionnaire used to measure patients' assessment of their own ability to function in normal activities. Answers to the 7 questions were rated on a 7 point scale in which 1 was very much worsened and 7 were very much improved since the start of the study. The seven functional areas are: * ability to go to work * ability to perform at work (includes both work outside the home and housework) * ability to walk * ability to exercise * ability to participate in social events * ability to have sex * ability to enjoy life
Patient Assessment of Function (PAF) at Week 12	Week 12 of the Double-blind Treatment Period	The PAF is a self-administered questionnaire used to measure patients' assessment of their own ability to function in normal activities. Answers to the 7 questions were rated on a 7 point scale in which 1 was very much worsened and 7 were very much improved since the start of the study. The seven functional areas are: * ability to go to work * ability to perform at work (includes both work outside the home and housework) * ability to walk * ability to exercise * ability to participate in social events * ability to have sex * ability to enjoy life
Patient Assessment of Function (PAF) at Endpoint	Endpoint of the Double-blind Treatment Period (up to week 12)	The PAF is a self-administered questionnaire used to measure patients' assessment of their own ability to function in normal activities. Answers to the 7 questions were rated on a 7 point scale in which 1 was very much worsened and 7 were very much improved since the start of the study. The seven functional areas are: * ability to go to work * ability to perform at work (includes both work outside the home and housework) * ability to walk * ability to exercise * ability to participate in social events * ability to have sex * ability to enjoy life Endpoint values are the last observed postbaseline data.
Clinician Global Impression of Severity (CGI-S) of Illness Scores During the Double-blind Treatment Period	Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period	The CGI-S is a clinician-rated scale that assesses the severity of the patient's pain condition and response to the treatment. Severity of illness, as related to moderate to severe pain, consists of the following 7 categories: * 1 normal-shows no sign of illness, * 2 borderline ill, * 3 mildly (slightly) ill, * 4 moderately ill, * 5 markedly ill, * 6 severely ill, and * 7 among the most extremely ill (Guy 1976). The clinician assesses the severity of the patient's condition, based on the clinician's total clinical experience with patients with this condition, in response to treatment. Endpoint values are the last observed postbaseline data.
Short-Form Health Survey (SF-36) Physical and Mental Component Summary Scores at Baseline, Week 12 and Endpoint	Baseline (end of Open-Label Titration Period), Week 12 and Endpoint (last visit up to week 12) of the Double-blind treatment period	SF-36 is a generic 36-item questionnaire measuring health-related quality of life (HRQL) covering 2 summary measures: physical component summary (PCS) and mental component summary (MCS). The SF-36 consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). PCS and MCS scores are constructed as a T-score with a mean of 50 and standard deviation of 10 and no minimum or maximum score; higher scores indicate better health status.
Brief Pain Inventory - Short Form (BPI-SF) Pain Interference Mean Score During the Double-Blind Treatment Period	Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, 12 and Endpoint (last visit up to week 12) of the Double-blind treatment period	For pain interference, the BPI-SF used numerical scales to measure how much pain had interfered with 7 daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others, and sleep in the past 24 hours. The scale used an 11 point Likert scale; range: 0 \[does not interfere\] to 10 \[completely interferes\]. BPI pain interference was typically scored as the mean of the 7 interference items. This mean could be used if at least 4 of 7 items had been completed on a given administration.
Participants With Adverse Events	Day 1 up to Day 52 in Open-Label Titration; Day 1 up to Day 128 in Double-Blind Treatment period	An adverse event (AE) was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an inability to carry out usual activities. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.
Participants With Potentially Clinically Significant Abnormal Vital Signs Values During the Double-Blind Treatment Period	Day 1 up to Day 128 in Double-Blind Treatment period	Data represents participants with potentially clinically significant (PCS) vital sign values. Significance criteria * Pulse - high: \>=120 and increase of \>= 15 beats/minute from baseline * Pulse - low: \<=50 and decrease of \>=15 beats/minute * Systolic blood pressure - high: \>=180 and increase \>=20 mmHg * Systolic blood pressure - low: \<=90 and decrease \>=20 mmHg * Diastolic blood pressure - high: \>=105 and increase of \>=15 mmHg * Diastolic blood pressure - low: \<=50 and decrease of \>=15 mmHg
Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period	Day 1 up to Day 128 in Double-Blind Treatment period	Data represents participants with potentially clinically significant abnormal serum chemistry, hematology and urinalysis values. Significance criteria: * Blood urea nitrogen: \>=10.71 mmol/L * Uric acid: M\>=625, F\>=506 μmol/L * Hemoglobin: M\<=115, F\<=95 g/dL * Hematocrit: M\<0.37, F\<0.32 % * Urinalysis: blood (hemoglobin) and total protein: \>=2 unit increase from baseline
Subjective Opiate Withdrawal Scales (SOWS) Scores During the Double-Blind Treatment Period	Weeks 1, 2, 4, 8, 12 and Endpoint (last visit up to Week 12) of the Double-blind treatment period	The results of the SOWS were collected in the e-diary daily during the first 4 weeks of the double blind treatment period and then during clinic visits at weeks 8 and 12 or early termination. The SOWS was a self administered questionnaire used to measure a participant's signs and symptoms of withdrawal from opiates. The scale contained 16 symptoms (eg, my nose is running; I feel restless), the participant rated the intensity on a scale of 0 (not at all) to 4 (extremely) for a total score of 0-64. The daily total score for the first 4 weeks was the largest score observed during the time period preceding that visit. For example, the week 1 score for each participant was the largest total score on any day between baseline and the night before the week 1 visit; the week 4 score for each participant was the largest score observed between the week 2 visit and the night before the week 4 visit.
Clinical Opiate Withdrawal Scales (COWS) Scores During the Double-Blind Treatment Period	Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, 12 and Endpoint (last visit up to Week 12) of the Double-blind treatment period	The COWS was a clinician rated scale used to measure a participant's signs and symptoms of withdrawal from opiates, with ratings based only on apparent relationship to withdrawal. The COWS was performed at day 0 and weeks 1, 2, 4, 8, and 12 (double blind treatment period) or early termination. The scale contained 11 signs/symptoms whose intensity the clinician rated on a scale of 0 to 4 or 5. A total score was calculated as the sum of the responses to the 11 signs/symptoms for a total range of 0-48. Withdrawal severity was classified, based on the total score, as follows: * 0 to 4=normal * 5 to 12=mild * 13 to 24=moderate * 25 to 36=moderately severe * \>36=severe
Addiction Behavior Checklist (ABC) Total Scores During Both the Open-Label Titration and Double-Blind Treatment Periods	Baseline for Open-Label Titration period, Baseline for Double-Blind Treatment period (which is also the end of the Open-Label Titration period), Weeks 1, 4, 8, 12, and Endpoint (last visit up to Week 12) of the Double-blind Treatment period	The ABC was a clinician rated scale that consisted of a brief (20 item) questionnaire designed to track behaviors characteristic of addiction related to prescription opioid medications in chronic pain populations. Items were focused on observable behaviors noted both during and between clinic visits. Each affirmative response was counted as one point, and points were added to calculate the total score, consequently resulting in scores ranging from 0 to 20 (0=no addiction-related behaviors seen and higher scores indicating an increasing number of addition-related behaviors seen). The ABC was to be performed at visits 2 and 7 (beginning and end of Open-label Titration period) and weeks 1, 4, 8, and 12 (Double-blind Treatment period) or early termination.
Current Opioid Misuse Measures (COMM) Total Scores During Both the Open-Label Titration and Double-Blind Treatment Periods	Baseline for Open-Label Titration period, Baseline for Double-Blind Treatment period (which is also the end of the Open-Label Titration period), Weeks 1, 4, 8, 12, and Endpoint (last visit up to Week 12) of the Double-blind Treatment period	The COMM was a clinician rated scale developed as a brief self report measure of current aberrant drug-related behavior for patients with chronic pain who were already on long term opioid therapy. A total score was calculated as the sum of the 17 questions. The total score ranged from 0 to 68. A score of 0 indicates no aberrant drug-related behaviors were seen. Patients with a total score of 9 or greater were classified as exhibiting aberrant drug-related behavior. The COMM was to be performed at visits 2 and 7 (beginning and end of Open-label Titration period) and weeks 1, 4, 8, and 12 (Double-blind Treatment period) or early termination.
Change From Baseline to Endpoint in the Double-Blind Treatment Phase in Electrocardiogram (ECG) Parameters	Baseline (end of Open-Label Titration Period), Endpoint (last visit up to Week 12) of the Double-blind treatment period	A 12-lead ECG was conducted at baseline and the last visit during the double-blind treatment period (week 12, or early termination).

Trial Locations

Locations (65): DCT-Sugarland, LLC
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Sugar Land, Texas, United States
Georgia Institute for Clinical Research, LLC
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Marietta, Georgia, United States
KRK Medical Research
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Dallas, Texas, United States
WK River Cities Clinical Research Center
🇺🇸
Shreveport, Louisiana, United States
Robert M. Karns, MD A Medical Corporation
🇺🇸
Los Angeles, California, United States
Medex Healthcare Research, Inc.
🇺🇸
Chicago, Illinois, United States
Rapid Medical Research
🇺🇸
Cleveland, Ohio, United States
International Research Associates, LLC
🇺🇸
Miami, Florida, United States
Accelovance, Inc.
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San Diego, California, United States
Clinical Research Center of Nevada
🇺🇸
Las Vegas, Nevada, United States
Sterling Research Group, Ltd.
🇺🇸
Cincinnati, Ohio, United States
Community Research, Inc
🇺🇸
Cincinnati, Ohio, United States
Lifetree Clinical Research
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Salt Lake City, Utah, United States
Radiant Research, Inc.
🇺🇸
Pinellas Park, Florida, United States
Horizon Research Group LLC
🇺🇸
Mobile, Alabama, United States
Physician Alliance Research Center
🇺🇸
Anaheim, California, United States
Associated Pharmaceutical Research Center, Inc.
🇺🇸
Buena Park, California, United States
Synergy Clinical Research
🇺🇸
Escondido, California, United States
Providence Clinical Research
🇺🇸
Burbank, California, United States
Research Center of Fresno, Inc.
🇺🇸
Fresno, California, United States
Pacific Coast Pain Management Center
🇺🇸
Laguna Hills, California, United States
Drug Studies America
🇺🇸
Marietta, Georgia, United States
Bayview Research Group, LLC
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Valley Village, California, United States
Avail Clinical Research, LLC
🇺🇸
DeLand, Florida, United States
Gold Coast Research LLC
🇺🇸
Plantation, Florida, United States
Sarasota Pain Medicine Research LLC
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Sarasota, Florida, United States
Radiant Research, Inc
🇺🇸
Greer, South Carolina, United States
Compass Research
🇺🇸
Orlando, Florida, United States
Community Research
🇺🇸
Crestview, Kentucky, United States
Better Health Clinical Research, Inc.
🇺🇸
Newnan, Georgia, United States
Millennium Pain Center
🇺🇸
Bloomington, Illinois, United States
Rehabilitation Associates of Indiana
🇺🇸
Indianapolis, Indiana, United States
International Clinical Research, Inc.
🇺🇸
Leawood, Kansas, United States
The Pain Treatment Center of the Bluegrass
🇺🇸
Lexington, Kentucky, United States
Horizon Research Group, LLC
🇺🇸
Baton Rouge, Louisiana, United States
HealthCare Research
🇺🇸
Florissant, Missouri, United States
Sundance Clinical Research, LLC
🇺🇸
Saint Louis, Missouri, United States
Beacon Clinical Research, LLC
🇺🇸
Brockton, Massachusetts, United States
Upstate Clinical Research Associates
🇺🇸
Williamsville, New York, United States
Meridian Clinical Research
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Omaha, Nebraska, United States
Wake Research Associates
🇺🇸
Raleigh, North Carolina, United States
Advanced Pain Consultants
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Voorhees, New Jersey, United States
Summit Research Network Inc.
🇺🇸
Portland, Oregon, United States
SP Research
🇺🇸
Oklahoma City, Oklahoma, United States
AMH Feasterville Family Health Care Center
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Trevose, Pennsylvania, United States
Pain Research of Oregon
🇺🇸
Eugene, Oregon, United States
Columbus Clinical Research
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Columbus, Ohio, United States
Trident Institute of Medical Research, LLC
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North Charleston, South Carolina, United States
South Carolina Pharmaceutical Research
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Spartanburg, South Carolina, United States
Greenville Pharmaceutical Research
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Greenville, South Carolina, United States
Renaissance Clinical Research & Hypertension of Texas, PLLC
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Dallas, Texas, United States
Medstar Clinical Research
🇺🇸
Houston, Texas, United States
Hillcrest Family Health Centers
🇺🇸
Waco, Texas, United States
Aspen Clinical Research, LLC
🇺🇸
Orem, Utah, United States
Radiant Research Inc.
🇺🇸
Anderson, South Carolina, United States
South Orange County Surgical Medical Group
🇺🇸
Laguna Hills, California, United States
Clinical Research of West Florida, Inc.
🇺🇸
Tampa, Florida, United States
MidAtlantic Pain Medicine Center
🇺🇸
Pikesville, Maryland, United States
Medex Healthcare Research Inc.
🇺🇸
Saint Louis, Missouri, United States
Tipton Medical and Diagnostic Center
🇺🇸
Tipton, Pennsylvania, United States
Clinical Research Center of Reading
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Wyomissing, Pennsylvania, United States
Radiant Research Dallas
🇺🇸
Dallas, Texas, United States
Brandywine Clinical Research
🇺🇸
Downingtown, Pennsylvania, United States
Omega Medical Research
🇺🇸
Warwick, Rhode Island, United States
Benchmark Research
🇺🇸
San Angelo, Texas, United States