An Efficacy and Safety Study of Sustained-release Paracetamol in Subjects With Osteoarthritis
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- GlaxoSmithKline
- Enrollment
- 960
- Locations
- 1
- Primary Endpoint
- Time-weighted Mean Change From Baseline in Western Ontario McMaster (WOMAC) Pain Through Week 12 of Treatment
Study Overview
Brief Summary
The purpose of the study is to determine whether paracetamol 1000 mg sustained-release (SR) tablets administered orally, twice daily are effective and safe in the treatment of patients with osteoarthritis of the knee or hip.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 40 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Male or female participants between 40 and 80 years of age
- •Diagnosis of moderate to moderately-severe osteoarthritis (OA) of either the knee or hip with respect to the following:
- •Pain in one knee/hip over 3 months immediately before screening visit
- •Use of non steroidal anti-inflammatory drugs (NSAIDs), acetaminophen (paracetamol) or any other analgesic for 3 or more days per week for at least 3 months prior to screening visit
- •Clinical diagnosis of osteoarthritis of knee/hip for minimum 6 month duration prior to screening visit
- •Therapeutic benefit with acetaminophen use with a score of ≥ 1 on 5-point categorical scale
- •Radiological evidence of ≥ Grade 2 osteoarthritis according to Kellgren-Lawrence radiographic criteria
- •Increased WOMAC Pain Subscale score of at least 20 % following untreated run-in period
- •Moderate to moderately-severe self-reported pain on a 5-point categorical scale following untreated run-in period
- •Historical self-reported positive therapeutic benefit with paracetamol use for osteoarthritis pain relief
Exclusion Criteria
- •History of surgery or major trauma to the study joint
- •Clinically significant signs or symptoms of inflammation upon completion of run-in period
- •Required ongoing use of analgesic therapy for other indications, anticoagulants, psychotherapeutic agents, aspirin at daily doses greater than 325 mg, statin-class hypolipidemic agents at doses that have not been stabilized, or other treatments know to interfere with pain perception
- •History of hepatic or renal or liver or biliary disease or gastrointestinal surgery
- •Participants with alanine aminotransferase (ALT) >2 times Upper Limit Normal (2xULN) and bilirubin > 1.5 times Upper Limit Normal (1.5xULN) (However, if direct bilirubin is <35% and fractioned, isolated bilirubin >1.5xULN is acceptable)
- •Other arthritis type, fibromyalgia or collagen vascular disease or secondary OA of study joint or chronic pain condition
Arms & Interventions
Paracetamol 2000 mg twice daily (BID)
Participants will be instructed to take two active paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces (~ 240 mL) of water/dose for 12 weeks.
Intervention: Paracetamol 1000 mg SR tablets (Drug)
Paracetamol 1330 mg thrice daily (TID)
Participants will be instructed to take two active paracetamol 665 mg SR tablets orally thrice daily (with 6-8 hours between adjacent doses) and two placebo to match paracetamol 1000 mg SR tablets orally twice daily (with 10-12 hours between adjacent doses) orally with approximately 8 ounces (~ 240 mL) of water/dose for 12 weeks.
Intervention: Paracetamol 665 mg SR tablets (Drug)
Placebo
Participants will be instructed to take two placebo to match paracetamol 1000 mg SR tablets twice daily (with 10-12 hours between adjacent doses) and two placebo to match paracetamol 665 mg SR tablets thrice daily (with 6-8 hours between adjacent doses) orally with approximately 8 ounces (~ 240 mL) of water/dose for 12 weeks.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Time-weighted Mean Change From Baseline in Western Ontario McMaster (WOMAC) Pain Through Week 12 of Treatment
Time Frame: Baseline up to week 12
The WOMAC Osteoarthritis Index is a 24-item questionnaire that assesses pain, physical function, and stiffness in the target joint. WOMAC Pain was measured using visual analogue scale (VAS) ranging from 0mm (no pain) to 100mm (extreme pain) at baseline and at week 1, 2, 4, 8, and 12. Lower values represent a better outcome. At each time point the assessment included 5 WOMAC Pain items: 1-walking on flat, 2-going up down stairs, 3-at night while in bed, 4-sitting or lying; 5-standing upright. Mean WOMAC Pain subscale score was calculated at each visit as the sum of 5 pain category scores divided by 5. Change from baseline was calculated for each visit as the mean WOMAC Pain subscale score minus the mean baseline WOMAC Pain subscale score. A negative change from Baseline indicated improvement. The time-weighted mean change was calculated as the area under the curve of change from baseline divided by the nominal time of the last on-therapy visit (week 12) from randomization (baseline).
Secondary Outcomes
- Time Weighted Mean Change From Baseline in WOMAC Physical Function Through Week 12 of Treatment(Baseline up to Week 12)
- Time Weighted Mean Change From Baseline in WOMAC Stiffness Through Week 12 of Treatment(Baseline up to week 12)
- Time-weighted Mean Change From Baseline in WOMAC Total Index Through Week 12 of Treatment(Baseline up to week 12)
- Mean Change From Baseline in Global Patient Assessment of Arthritis (GPAOA)(Baseline, Week 4, Week 8, Week 12)
- Number of Participants Classified as Responder(Baseline, Week 12)
- Mean Change From Baseline in Daily Pain, Daily Stiffness and Pain/Stiffness (Composite) at Week 12(Baseline, Week 12)
- Mean Number of Rescue Medication Pills Taken Per Day up to 12 Weeks(every day up to 12 weeks)
- Mean Change From Baseline in Chronic Pain Sleep Inventory (CPSI)(Baseline, Week 4, Week 8, Week 12)
- Patient Global Assessment of Response to Therapy (PGART)(Week 4, Week 8, Week 12)