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Study to Evaluate the Long-Term Safety of Hydrocodone Bitartrate Extended-Release Tablets (CEP-33237) in Patients Who Require Opioid Treatment for an Extended Period of Time

2 de mayo de 2017 actualizado por: Teva Branded Pharmaceutical Products R&D, Inc.

A 12-Month, Open-Label Study to Evaluate the Long-Term Safety of Hydrocodone Bitartrate Extended-Release Tablets (CEP-33237) at 15 to 90 mg Every 12 Hours in Patients Who Require Opioid Treatment for an Extended Period of Time

The primary objective of this study is to evaluate the safety of hydrocodone extended-release tablets when used over a 12-month period in patients with chronic pain, as assessed by adverse events, clinical laboratory results, vital signs measurements, electrocardiogram results, physical examination findings, pure tone audiometry, and concomitant medication usage.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

This was a Phase 3, open-label, nonrandomized study that consisted of a screening period, an open label titration period, and a 52 week, long term, open-label treatment period in patients with chronic pain. Patients were eligible to participate in this study if they had completed study C33237/3079 (NCT01240863) (these patients are hereafter referred to as rollover patients) or if they had not participated in study 3079 (these patients are hereafter referred to as either new opioid naïve or new opioid experienced patients).

Tipo de estudio

Intervencionista

Inscripción (Actual)

330

Fase

  • Fase 3

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • Estados Unidos
    • Alabama
      • Mobile, Alabama, Estados Unidos
        • Horizon Research Group, LLC
    • California
      • Anaheim, California, Estados Unidos
        • Physician Alliance Research Center
      • Beverly Hills, California, Estados Unidos
        • Adam D. Karns, MD
      • Buena Park, California, Estados Unidos
        • Associated Pharmaceutical Research Center, Inc.
      • Burbank, California, Estados Unidos
        • Providence Clinical Research
      • Fresno, California, Estados Unidos
        • Research Center of Fresno, Inc.
      • Laguna Hills, California, Estados Unidos
        • Pacific Coast Pain Management Center
      • Laguna Hills, California, Estados Unidos
        • South Orange County Surgical Medical Group
      • San Diego, California, Estados Unidos
        • Accelovance, Inc.
      • Valley Village, California, Estados Unidos
        • Bayview Research Group, LLC
    • Florida
      • Clearwater, Florida, Estados Unidos
        • Clinical Research of West Florida, Inc.
      • DeLand, Florida, Estados Unidos
        • Avail Clinical Research, LLC
      • Orlando, Florida, Estados Unidos
        • Compass Research, LLC
      • Sarasota, Florida, Estados Unidos
        • Sarasota Pain Medicine Research LLC
      • Weston, Florida, Estados Unidos
        • Gold Coast Research LLC
    • Georgia
      • Marietta, Georgia, Estados Unidos
        • Drug Studies America
      • Marietta, Georgia, Estados Unidos
        • Georgia Institute for Clinical Research, LLC
      • Marietta, Georgia, Estados Unidos
        • Taylor Research, LLC
      • Newnan, Georgia, Estados Unidos
        • Better Health Clinical Research, Inc.
    • Illinois
      • Bloomington, Illinois, Estados Unidos
        • Millennium Pain Center
    • Indiana
      • Indianapolis, Indiana, Estados Unidos
        • Rehabilitation Associates of Indiana
    • Kansas
      • Overland Park, Kansas, Estados Unidos
        • International Clinical Research, Inc.
    • Kentucky
      • Crestview Hills, Kentucky, Estados Unidos
        • Community Research
    • Louisiana
      • Shreveport, Louisiana, Estados Unidos
        • Willis Knighton River Cities Clinical Research Center
    • Maryland
      • Pikesville, Maryland, Estados Unidos
        • MidAtlantic Pain Medicine Center
    • Massachusetts
      • Brockton, Massachusetts, Estados Unidos
        • Beacon Clinical Research, LLC
    • Missouri
      • Florissant, Missouri, Estados Unidos
        • HealthCare Research
      • Saint Louis, Missouri, Estados Unidos
        • Sundance Clinical Research, LLC
    • Nebraska
      • Omaha, Nebraska, Estados Unidos
        • Meridian Clinical Research
    • Nevada
      • Las Vegas, Nevada, Estados Unidos
        • Clinical Research Center of Nevada
    • New Jersey
      • Voorhees, New Jersey, Estados Unidos
        • Advanced Pain Consultants
    • New York
      • Williamsville, New York, Estados Unidos
        • Upstate Clinical Research Associates
    • North Carolina
      • Raleigh, North Carolina, Estados Unidos
        • Wake Research Associates
    • Ohio
      • Cincinnati, Ohio, Estados Unidos
        • Sterling Research Group, Ltd.
      • Columbus, Ohio, Estados Unidos
        • Columbus Clinical Research
    • Oklahoma
      • Oklahoma City, Oklahoma, Estados Unidos
        • SP Research
    • Oregon
      • Eugene, Oregon, Estados Unidos
        • Pain Research of Oregon
      • Portland, Oregon, Estados Unidos
        • Summit Research Network Inc.
    • Pennsylvania
      • Downingtown, Pennsylvania, Estados Unidos
        • Brandywine Clinical Research
      • Feasterville-Trevose, Pennsylvania, Estados Unidos
        • AMH Feasterville Family Health Care Center
      • Tipton, Pennsylvania, Estados Unidos
        • Tipton Medical and Diagnostic Center
      • West Reading, Pennsylvania, Estados Unidos
        • Clinical Research Center of Reading, LLP
    • Rhode Island
      • Warwick, Rhode Island, Estados Unidos
        • Omega Medical Research
    • South Carolina
      • Greenville, South Carolina, Estados Unidos
        • Greenville Pharmaceutical Research
      • North Charleston, South Carolina, Estados Unidos
        • Trident Institute of Medical Research, LLC
      • Spartanburg, South Carolina, Estados Unidos
        • S. Carolina Pharmaceutical Research
    • Texas
      • Dallas, Texas, Estados Unidos
        • KRK Medical Research
      • Dallas, Texas, Estados Unidos
        • Radiant Research
      • Dallas, Texas, Estados Unidos
        • Renaissance Clinical Research & Hypertension of Texas, PLLC
      • Houston, Texas, Estados Unidos
        • MedStar Clinical Research
      • San Angelo, Texas, Estados Unidos
        • Benchmark Research
      • Sugar Land, Texas, Estados Unidos
        • DCT-Sugarland, LLC dba Discovery Clinical Trials
      • Waco, Texas, Estados Unidos
        • Hillcrest Family Health Centers
    • Utah
      • Orem, Utah, Estados Unidos
        • Aspen Clinical Research, LLC

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años a 80 años (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  • The patient must be willing and able to successfully self-administer the study drug, comply with study restrictions, and return to the clinic for scheduled study visits as specified in this protocol.
  • The patient has either completed Cephalon study 3079 or has chronic pain of at least 3 months duration prior to entering this study associated with any of the following conditions: diabetic peripheral neuropathy, postherpetic neuralgia, traumatic injury, complex regional pain syndrome, back pain, neck pain, osteoarthritis, or rheumatoid arthritis. Patients with other painful conditions may qualify for the study with permission from the Cephalon medical monitor or designee.
  • Those patients who completed the 12-week, double-blind, placebo-controlled, randomized study (study 3079) and are willing to re-titrate study drug to an effective dose of hydrocodone extended-release tablets are eligible to enter this study.
  • The patient is able to speak English, willing to provide written informed consent, and sign a written opioid agreement, to participate in this study.
  • The patient is 18 through 80 years of age (inclusive) at the time of entering this or the previous study (study 3079).
  • 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.

Exclusion Criteria:

  • Patients who were enrolled in study 3079 but did not complete the 12-week, double-blind, placebo-controlled, randomized study may not be enrolled into this study.
  • The patient has known or suspected hypersensitivities, allergies, or other contraindications to the study drug or its excipients.
  • The patient has a recent history (within 5 years) or current evidence of alcohol or other substance abuse.
  • The patient has a medical or psychiatric condition/disease that, in the opinion of the investigator, would compromise collected data.
  • The patient is taking a total (i.e., including around-the clock [ATC] and rescue medications) of more than 135 mg/day of oxycodone or equivalent for 14 days prior to screening.
  • The patient has a history of suicidality.
  • The patient has a diagnosis of chronic headache or migraine as the primary painful condition under study.
  • The patient is expected to have surgery during the study and it is anticipated that the surgery will alleviate the patient's 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 potent synthetic opioids.
  • The patient has participated in a study involving an investigational drug in the previous 30 days (excluding those who participated in study 3079).
  • 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 chronic pain currently being treated.
  • The patient has a positive urine drug screen (UDS) for an illicit substance or medication not prescribed by the physician currently treating the chronic pain.
  • The investigator feels that the patient is not suitable for the study.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: N / A
  • Modelo Intervencionista: Asignación de un solo grupo
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Hydrocodone ER
Participants were titrated (or re-titrated for roll-over participants) at escalating dosages of extended-release hydrocodone tablets at dosages of 15, 30, 45, 60, or 90 mg orally every 12 hours until deemed successful for managing their pain during the open-label titration period. Once a successful dose was identified, participants entered the 52 week open-label treatment period in which hydrocodone ER was administered at the successful dose (15, 30, 45, 60, or 90 mg) every 12 hours.
Droga: Hydrocodone ER
Hydrocodone bitartrate extended-release tablets were administered at doses of 15, 30, 45, 60, and 90 mg orally every 12 hours. During the open-label titration period, doses were adjusted until a stable pain control was achieved. In general, the dose of hydrocodone extended release tablets could be adjusted for efficacy or tolerability, as necessary, at any time during the open-label treatment period; however, participants were required to visit the study center before increasing the dose of study drug.
Otros nombres:
  • CEP-33237
  • Bitartrato de hidrocodona de liberación prolongada

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Participants With Adverse Experiences
Periodo de tiempo: Day 1 of open-label titration period - Week 52 of the open-label 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. 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.
Day 1 of open-label titration period - Week 52 of the open-label treatment period
Participants With Potentially Clinically Significant (PCS) Abnormal Laboratory Values During the Open-Label Treatment Period by Participant Status
Periodo de tiempo: Day 1 - Week 52 of the open-label treatment period

Data represents participants with PCS abnormal serum chemistry, hematology and urinalysis values.

Significance criteria:

  • alanine aminotransferase (ALT): >=3 times the upper limit of normal (ULN). Normal range is 6-43 U/L
  • aspartate aminotransferase (AST): >=3 times ULN. Normal range is 9-36 U/L
  • blood urea nitrogen (BUN): >=10.71 mmol/L
  • creatinine: >=177 μmol/L
  • uric acid: M>=625, F>=506 μmol/L
  • white blood cell count: <=3.0*10^9/L
  • hemoglobin: M<=115, F<=95 g/dL
  • hematocrit: M<0.37, F<0.32 L/L
  • urine blood (hemoglobin): >=2 unit increase from baseline
  • urine glucose: >=2 unit increase from baseline
Day 1 - Week 52 of the open-label treatment period
Participants With Potentially Clinically Significant Abnormal Vital Signs Values by Participant Status
Periodo de tiempo: Day 1 of open-label titration period - Week 52 of the open-label 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
Day 1 of open-label titration period - Week 52 of the open-label treatment period
Shifts in Electrocardiogram (ECG) Findings From Baseline to Overall Study by Participant Status
Periodo de tiempo: Baseline for new participants was between Day -7 and -14 (the study 3080 screening visit); baseline for rollover participants was the last ECG in study 3079. During study ECGs were performed on weeks 24 and 52 of the open-label treatment period

A 12-lead ECG was conducted at screening, week 24, and week 52 or at the last postbaseline observation. For rollover participants, the ECG performed at the final visit of study 3079 served as the 1st ECG in study 3080. A qualified physician was responsible for interpreting the ECG. Any ECG finding that was judged by the investigator as a clinically meaningful change (worsening) compared with baseline was considered an adverse event.

For overall results, the worst postbaseline finding for the participant was summarized.

Results below are formatted as Baseline ECG result - Overall ECG result.
Baseline for new participants was between Day -7 and -14 (the study 3080 screening visit); baseline for rollover participants was the last ECG in study 3079. During study ECGs were performed on weeks 24 and 52 of the open-label treatment period
Participants With Clinically Significant (CS) Hearing Changes From Baseline in Pure Tone Audiometry Test Results by Patient Status
Periodo de tiempo: Baseline for new participants was between Day -7 and -14 (study 3080 screening visit); baseline for rollover participants was the baseline test in study 3079. During study covers both open-label titration and 52-week treatment periods
Pure tone audiometry was performed by trained personnel. During the test, the patient wore headphones and was seated in a quiet room; trained personnel manipulated the audiometry equipment to test the patient's hearing. For serial audiograms, the criteria for a clinically significant (CS) hearing change were based on the guidance from the American Speech-Language Hearing Association (ASHA) 1994 (Konrad-Martin et al 2005). These criteria included the following: greater than 20 decibels (dB) pure tone threshold shift at 1 frequency; greater than 10 dB shift at 2 consecutive test frequencies; or threshold response shifting to "no response" at 3 consecutive test frequencies.
Baseline for new participants was between Day -7 and -14 (study 3080 screening visit); baseline for rollover participants was the baseline test in study 3079. During study covers both open-label titration and 52-week treatment periods

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Participant Global Assessment (PGA) of the Method of Pain Control by Participant Status
Periodo de tiempo: Baseline for new participants was Day 1, i.e. the first day of open-label titration. Baseline for rollover participants was the baseline in study 3079. Week 4 (end of titration, start of open-label treatment), Week 52, last visit up to Week 52
The PGA of the method of pain control consisted of a asking patients a single question to assess their method of pain control during the previous 24 hours as either poor, fair, good, or excellent (Rothman et al 2009).
Baseline for new participants was Day 1, i.e. the first day of open-label titration. Baseline for rollover participants was the baseline in study 3079. Week 4 (end of titration, start of open-label treatment), Week 52, last visit up to Week 52
Participants by Risk Category for Aberrant Drug Misuse Based on the Total Score in the Screener and Opioid Assessment for Patients With Pain - Revised (SOAPP-R)
Periodo de tiempo: End of Open-label Titration Period. Weeks 4 and 24 of the Open-label Treatment Period

SOAPP-R is a clinician-rated scale used to assess each patient's risk of developing aberrant drug use behaviors while on long term opioid therapy. SOAPP-R consists of 24 questions that address 8 concepts: substance abuse history, medication related behaviors, antisocial behaviors/history, psychosocial problems, psychiatric history, physician patient relationship factors, emotional attachment to pain medications, and personal care and lifestyle issues (Butler et al 2008). Each question is answered using a 5 point Likert-like scale, with 0=never, 1=seldom, 2=sometimes, 3=often, and 4=very often for a total range of 0-96. The higher the overall score, the greater the probability the patient is at risk for displaying aberrant behaviors consistent with drug use.

An overall score of 18 or higher is considered positive for predicting aberrant drug related behavior, therefore the reported risk categories are

  • <18 and
  • <=18. Results indicate timeframe followed by risk cat
End of Open-label Titration Period. Weeks 4 and 24 of the Open-label Treatment Period
Addiction Behavior Checklist (ABC) Total Scores During Both the Open-Label Titration and Open-Label Treatment Periods by Participant Status
Periodo de tiempo: Baseline for new participants was Day 1 of open-label titration; rollover participants baseline was in study 3079. End of Open-label Titration: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 40, 44, 48, 52 and last visit up to week 52
The ABC was a clinician rated scale that consisted of a brief (21 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 1 point, and points were added to calculate the total score. All but 1 of the 21 items (the provider's impression) was used in calculating 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). Participants with a total score of 3 or greater were classified as exhibiting inappropriate opioid use during the study.
Baseline for new participants was Day 1 of open-label titration; rollover participants baseline was in study 3079. End of Open-label Titration: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 40, 44, 48, 52 and last visit up to week 52
Current Opioid Misuse Measure (COMM) Scores During Both the Open-Label Titration and Open-Label Treatment Periods by Participant Status
Periodo de tiempo: Baseline for new participants was Day 1 of open-label titration; rollover participants baseline was in study 3079. End of Open-label Titration Period. Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 40, 44, 48, 52 and last visit up to week 52
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.
Baseline for new participants was Day 1 of open-label titration; rollover participants baseline was in study 3079. End of Open-label Titration Period. Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 40, 44, 48, 52 and last visit up to week 52

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Teva Branded Pharmaceutical Products R&D, Inc.

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de octubre de 2010

Finalización primaria (Actual)

1 de septiembre de 2012

Finalización del estudio (Actual)

1 de septiembre de 2012

Fechas de registro del estudio

Enviado por primera vez

15 de octubre de 2010

Primero enviado que cumplió con los criterios de control de calidad

18 de octubre de 2010

Publicado por primera vez (Estimar)

19 de octubre de 2010

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

5 de junio de 2017

Última actualización enviada que cumplió con los criterios de control de calidad

2 de mayo de 2017

Última verificación

1 de mayo de 2017

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • C33237/3080

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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