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Long-term Safety of Once-daily Hydrocodone Bitartrate (HYD) Tablets For Moderate to Severe Chronic Nonmalignant and Nonneuropathic Pain. Includes a 24-week Extension Period.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Purdue Pharma LP
ClinicalTrials.gov Identifier:
NCT01400139
First received: July 20, 2011
Last updated: December 12, 2014
Last verified: December 2014
  Purpose

The primary objective of this study is to characterize the long-term safety of Hydrocodone Bitartrate (HYD) tablets 20 to 120 mg once-daily in subjects with chronic nonmalignant and nonneuropathic pain.


Condition Intervention Phase
Chronic Nonmalignant and Nonneuropathic Pain
Drug: Hydrocodone bitartrate q24h film-coated tablets
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Multicenter Study to Assess the Long -Term Safety of Hydrocodone Bitartrate (HYD) Tablets 20 to 120 mg Once-daily in Subjects With Moderate to Severe Chronic Nonmalignant and Nonneuropathic Pain

Resource links provided by NLM:


Further study details as provided by Purdue Pharma LP:

Primary Outcome Measures:
  • The Number of Participants With Adverse Events as a Measure of Safety [ Time Frame: Up to 84 weeks ] [ Designated as safety issue: No ]
    Safety assessments included AEs, clinical laboratory test results, vital sign measurements, ECG findings, and audiology assessments.

  • Daily "Average Pain Over the Last 24 Hours" [ Time Frame: Core study: from start to end of maintenance period (up to 52 weeks); Extension study: from start of maintenance to end of extension (up to 76 weeks) ] [ Designated as safety issue: No ]
    "Average pain over the last 24 hours" score (on an 11-point numerical rating scale where 0 = no pain and 10 = pain as bad as you can imagine).


Secondary Outcome Measures:
  • "Pain Right Now" Score [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    "Pain right now" scores were collected using an 11-point scale where 0 = no pain and 10 = pain as bad as you can imagine. The "pain right now" scores were only collected during the Core Study. "Pain right now" scores were not assessed during the Extension Period.

  • Medical Outcomes Study (MOS) Sleep Scale - Revised (MOS Sleep-R) [ Time Frame: Up to 52 weeks in the Core Study maintenance period, and up to 24 weeks in the Extension Period ] [ Designated as safety issue: No ]
    The MOS Sleep-R is a brief, self-administered 12-item assessment designed to measure key aspects of sleep: sleep problems index II and 6 subscale scores - sleep disturbance, sleep adequacy, daytime somnolence, snoring, awaken short of breath or with headache, and quantity of sleep. For the derived scores in the MOS Sleep-R, a higher score indicates a better sleep pattern.

  • Brief Pain Inventory Short Form (BPI-SF) - Pain Interference [ Time Frame: Up to 52 weeks in maintenance and up to 24 weeks in extension ] [ Designated as safety issue: No ]
    The BPI-SF questionnaire was used to assess the severity of pain and the interference of pain on daily functions. It consists of 9 sections that measure pain location, intensity, pain treatment, and functional interference of pain on mood and every day activities. Four of the items (questions 3 through 6) assess the severity of pain and 7 items (questions 9A through 9G) assess the interference of pain. The pain severity subscale was determined by calculating the arithmetic mean of the responses to items 3, 4, 5 and 6. For BPI, a lower score indicates a lower pain.

  • Medical Outcomes Study 36-item Short Form (SF-36) [ Time Frame: Up to 52 weeks in maintenance and up to 24 weeks in extension ] [ Designated as safety issue: No ]
    The SF-36 is a generic health survey with 36 items that measure functional health and well-being from the subject's perspective. The 36 questions are grouped into 11 sections. Some of the sections consist of multiple questions. The survey is summarized into 8 dimensions/scales: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. From the 8 health dimensions, physical component summary, and mental component summary measures are derived. For SF-36, a higher score indicates a better perception of health.

  • Patient Global Impression of Change (PGIC) [ Time Frame: At Week 52 in maintenance and at Week 24 in extension ] [ Designated as safety issue: No ]
    The PGIC is an ordinal scale of global evaluation that assesses the change in overall status relative to the start of the study. The scale has only 1 item that measures global change of overall status (improvement or worsening) by the subject on a 7-point scale (Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse. The proportion of subjects with a response of "much improved" (category 2) and "very much improved" (category 1), is provided along with 95% confidence intervals for the proportion.

  • Treatment Satisfaction Questionnaire (TSQ) - Part I [ Time Frame: At Week 52 or upon early discontinuation at or before Week 4 in maintenance ] [ Designated as safety issue: No ]
    The TSQ is a self-administered questionnaire that consists of 2 parts. Part I has 6 questions (Q1 to Q6) that ask the subject to rate the experience with use of the study drug in comparison to the prestudy pain medication regarding ease of use, convenience, frequency, pain control, and overall satisfaction. Each question was rated on a scale from 1 (extremely satisfied) to 6 (extremely dissatisfied): Q1=Satisfaction with study drug; Q2=Ease of study drug use to treat pain; Q3=Convenience of study drug to treat pain; Q4=Overall drug satisfaction managing pain; Q5=Satisfaction with frequency of use; Q6=Ease of planning study drug use. TSQ - Part I was not administered in the extension period.

  • Treatment Satisfaction Questionnaire (TSQ) - Part II [ Time Frame: At Week 52 or upon early discontinuation at or before Week 4 in maintenance and at Week 24 in extension ] [ Designated as safety issue: No ]
    The TSQ is a self-administered questionnaire that consists of 2 parts. Part II has 2 questions that measure the subject's willingness to continue the use of study drug as pain medication (Q1), and to recommend the study drug to someone else (Q2). Question 1 consists of 6 categories of response rated on a scale from 1 (very willing to continue) to 6 (very unwilling to continue): 1=Very willing to continue; 2=Willing to continue; 3=Somewhat willing to continue; 4=Somewhat unwilling to continue; 5=Unwilling to continue; 6=Very unwilling to continue. Question 2 consists of 3 categories of response: 1=yes; 2=no; 3=undecided.


Enrollment: 922
Study Start Date: July 2011
Study Completion Date: October 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hydrocodone bitartrate
Hydrocodone bitartrate (HYD) once daily (q24h) tablets
Drug: Hydrocodone bitartrate q24h film-coated tablets
Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
Other Name: Hysingla ER

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria include:

  • Male and female subjects ≥ 18 years of age with moderate to severe, chronic nonmalignant and nonneuropathic pain (lasting several hours daily) as their predominant pain condition for at least 3 months prior to the screening visit;
  • Subjects deemed by the investigator/medically qualified designee (must be MD or DO) to be appropriate candidates for the protocol specified, around the clock HYD therapeutic regimen;
  • Female subjects who are premenopausal or postmenopausal less than 1 year and who have not had surgical sterilization (ie, tubal ligation, partial or complete hysterectomy) must have a negative serum pregnancy test, be nonlactating, and willing to use adequate and reliable contraception throughout the study (eg, barrier with additional spermicidal foam or jelly, intra-uterine device, hormonal contraception);
  • Subjects who are willing and able to be compliant with the protocol, are capable of subjective evaluation (ie pain scores), are able to read and understand questionnaires, are willing and able to use an electronic diary, and are able to read, understand, and sign the written informed consent form in English.

Exclusion Criteria include:

  • Subjects taking opioid analgesic(s) equivalent to > 120 mg/day of oxycodone during the 14 days prior to the screening visit;
  • Subjects who previously participated in an investigational hydrocodone study within 90 days prior to the first dose of study medication ;
  • Subjects who have used any investigational medication other than hydrocodone within 30 days prior to the first dose of study drug;
  • Subjects with any history of seizures (subjects with history of pediatric febrile seizures may participate in the study) or increase in intracranial pressure;
  • Subjects with current uncontrolled depression or other uncontrolled psychiatric disorder (subjects with controlled depression or other psychiatric disorder must be on a stable medication for ≥ 1 month prior to the screening visit to participate in the study);
  • Subjects with a history of alcohol, medication, or illicit drug abuse or addiction and/or history of opioid abuse or addiction at any time;
  • Subjects with clinically unstable cardiac disease, including: unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling pacemaker;
  • Subjects with unstable respiratory disease that, in the opinion of the investigator, precludes entry into this study;
  • Subjects with biliary tract disease, hypothyroidism, adrenal cortical insufficiency, or any other medical condition that, in the opinion of the investigator, is inadequately treated and precludes entry into the study;
  • Subjects with history of malignancy within past 2 years, with exception of basal cell carcinoma that has been successfully treated;
  • Subjects with evidence of impaired liver function upon entry into the study (laboratory test values ≥ 3 times the upper limit of the laboratory reference (normal) range (ULN) for aspartate transaminase [AST/SGOT] or alanine transaminase [ALT/SGPT], or values > 2 times the ULN for alkaline phosphatase), or total bilirubin level > 1.5 times the ULN or, in the opinion of the investigator/medically qualified designee (must be MD or DO), liver function impairment to the extent that the subject should not participate in this study;
  • Subjects with evidence of impaired kidney function upon entry into the study (ie, serum creatinine ≥ 2.5 mg/dL);
  • Subjects with any condition in which opioids are contraindicated, eg, severe respiratory depression with hypoxia and/or hypercapnia, severe chronic obstructive lung disease, cor pulmonale, severe bronchial asthma, or paralytic ileus;
  • Subjects who are allergic to hydrocodone or who have a history of allergies to other opioids. This does not include subjects who have experienced common opioid side effects (eg, nausea, constipation);
  • Subjects receiving monoamine oxidase inhibitors (MAOIs) or who have been taking MAOIs within 2 weeks of the screening visit.

Other protocol-specific inclusion/exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01400139

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Sponsors and Collaborators
Purdue Pharma LP
  More Information

Additional Information:
No publications provided

Responsible Party: Purdue Pharma LP
ClinicalTrials.gov Identifier: NCT01400139     History of Changes
Other Study ID Numbers: HYD3003
Study First Received: July 20, 2011
Results First Received: December 1, 2014
Last Updated: December 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Purdue Pharma LP:
Pain
Nonmalignant pain
Nonneuropathic Pain
Opioid

Additional relevant MeSH terms:
Hydrocodone
Analgesics
Analgesics, Opioid
Antitussive Agents
Central Nervous System Agents
Central Nervous System Depressants
Narcotics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 27, 2015