An Efficacy Study of Combination of Tramadol and Acetaminophen Tablets in the Treatment of Participants With Fibromyalgia Pain

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the analgesic effect of combination of tramadol hydrochloride and acetaminophen in participants for treatment of fibromyalgia pain (chronic widespread pain and presence of tender points).

Detailed Description
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This is an open-label (all people know the identity of the intervention) and multi-center (conducted in more than one center) study of combination of tramadol hydrochloride and acetaminophen in treatment of participants with pain of fibromyalgia. The duration of this study will be 56 days per participant. The study consists of 2 parts: Screening (that is, 3 weeks before study commences on Day 1) and Treatment (that is, up to Day 56). All the eligible participants will receive oral tablet for combination of tramadol hydrochloride and acetaminophen. Rescue medication (a medication intended to relieve symptoms immediately) of tylenol (500 milligram, up to 6 oral tablets daily) will be permitted throughout the study duration. Efficacy of the participants will primarily be evaluated by Pain Visual Analog Scale. Participants' safety will be monitored throughout the study.

Official Title
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Ultracet (Tramadol HCL [37.5 mg]/Acetaminophen [325 mg]) Combination Tablets in the Treatment of the Pain of Fibromyalgia

Conditions
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Pain, Fibromyalgia

Intervention / Treatment
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* Drug: Tramadol hydrochloride
* Drug: Acetaminophen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must meet the American College of Rheumatology 1990 criteria for the classification of fibromyalgia (that are, Participants must have had widespread pain [pain in three quadrants and in the axial skeleton] for at least three months and pain on digital palpation in 11 or more of the 18 tender-point sites Female participants must not be pregnant, breast feeding or postmenopausal for at least one year Participant must be able to take oral medication Participants must have completed the Screening or wash-out procedures and have a visual analog scale score greater than or equal to 40 milliliter Fail to non-opioid analgesics Exclusion Criteria: Participants who previously failed tramadol hydrochloride therapy or those who discontinued tramadol hydrochloride due to adverse events Participants diagnosed with either any active connective tissue or musculo-skeletal diseases, or malignancy or history of malignancy within past 5 years, or painful, symptomatic osteoarthritis, or regional periarticular pain syndromes, spondyloarthropathy and major endocrine disease Participants who currently have more severe pain than the pain of fibromyalgia Participants who have taken antidepressants, cyclobenzaprine or anti-epileptic drugs for pain within three weeks of the Treatment Phase Participants who have taken short-acting analgesics, topical medications and anesthetics and/or muscle relaxants for a period of less than 21 days of the given medication prior to the Treatment Phase

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tramadol hydrochloride/acetaminophen<br>Tramadol hydrochloride/acetaminophen oral tablet will be administered as 37.5 /325 milligram respectively once daily for Day 1-3, twice daily for Day 4-6 and thrice daily for Day 7-56. | Drug: Tramadol hydrochloride<br>* Tramadol hydrochloride oral tablet will be administered at a dose of 37.5 milligram as, once daily for Day 1-3, twice daily for Day 4-6 and thrice daily for Day 7-56.<br>Drug: Acetaminophen<br>* Acetaminophen oral tablet will be administered at a dose of 325 milligram as, once daily for Day 1-3, twice daily for Day 4-6 and thrice daily for Day 7-56.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Visual Analog Scale Score at Day 14 | Pain visual analog scale was used to assess the amount of pain recently experienced (within the last 48 hours) by marking a slash through the line of a 100 millimeter (mm) scale measuring pain from no pain (0 mm) to worst possible pain (100 mm). | Day 14 | 
| Pain Visual Analog Scale Score at Day 28 | Pain visual analog scale was used to assess the amount of pain recently experienced (within the last 48 hours) by marking a slash through the line of a 100 millimeter (mm) scale measuring pain from no pain (0 mm) to worst possible pain (100 mm). | Day 28 | 
| Pain Visual Analog Scale Score at Day 56 | Pain visual analog scale was used to assess the amount of pain recently experienced (within the last 48 hours) by marking a slash through the line of a 100 millimeter (mm) scale measuring pain from no pain (0 mm) to worst possible pain (100 mm). | Day 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Categorical Scores on Pain Relief Rating Scale | Pain Relief Rating Scale was used to measure the amount of pain relief experienced (on average) relative to the no-medication Screening or wash-out phase using a 6-point Likert scale ranging from (-) 1 to 4 and rated as (-) 1=worse, 0=None, 1=Slight, 2=moderate,3=a lot and 4=complete. | Day 14, 28 and 56 | 
| Tender-Point Evaluation/ Myalgic Score | Eighteen tender-point sites were evaluated by digital palpation for pain by the same Investigator at each site. The Investigator rated the participant's response to digital palpation on a scale from 0 (no pain [participant did not have a tender point]) to 3 (participant withdrawn or flinched). Total myalgic score was the sum of tender-point pain ratings.The total tender-Point score ranges from 0 to 18, and the total myalgic score ranges from 0 to 54. Higher score indicates worsening. | Baseline and Day 56 | 
| Sleep Questionnaire: Number of Hours to Fall Asleep and Participant Slept | The patient assessment sleep questionnaire consisted of 12-Questions (Q) to evaluate the participant's sleep habits out of which Q1 was How long did it usually take for participant to fall asleep during the past 4 weeks and Q2 was On the average, how many hours did participant sleep each night during the past 4 weeks. | Baseline and Day 56 | 
| Participant Assessment Sleep Questionnaire Score | Sleep questionnaire consisted of 12-Questions (Q), Q3-Q12 were related to How often during past 4 weeks did participant felt and are as: Q3: sleep not quiet, Q4: get enough sleep to feel rested upon waking in morning, Q5: awaken short of breath or with headache, Q6: feel drowsy or sleepy, Q7: have trouble falling asleep, Q8: awaken during sleep time and have trouble falling asleep again, Q9: trouble staying awake during day, Q10: snore, Q11: take naps during day, Q12: get amount of sleep needed. Score ranged from 1= all the time to 6 = none of the time, higher score indicates improvement. | Baseline and Day 56 | 
| Total Fibromyalgia Impact Questionnaire (FIQ) Score | The FIQ was 19-item questionnaire which measured participant status, progress and outcomes. First 10 items made up of a physical functioning scale, ranging from 0 (always) to 3 (never). Items 11 and 12 asked participants to mark the number of days they felt well (0-7 days) and missed work (0-5 days). Items 13-19 were measured using 10 centimeter (cm) visual analog scale, score ranging from 0 cm (no) to 10 cm (very). Total FIQ score ranged from 0 -100 which was calculated as sum of final scores for item 1-10, 11 and 12, and individual score for item 13-19, and higher score indicates worsening. | Baseline and Day 56 | 
| Number of Participants With Physician Global Assessment | The treating physician rated the participant's condition on Day 1 before the start of treatment and each return visit. The assessment included how the drug controlled the pain (Question 1 [Q1]), adverse event (Question 2 [Q2]), and overall evaluation (Question 3 [Q3]), and participant's condition was indicated as very good, good, moderate, poor and very poor. | Day 14, 28 and 56 | 
| Number of Participants With Subject's Global Assessment | Participants indicated their condition on Day 1 before the start of treatment and each return visit. The assessment included how the drug controlled the pain (Question 1 [Q1]), adverse event (Question 2 [Q2]), and overall evaluation (Question 3 [Q3]), and participants indicated their condition as very good, good, moderate, poor and very poor. | Day 14, 28 and 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Fibromyalgia, Ultracet, Tramadol Hydrochloride, Acetaminophen