A 12-Week Efficacy Study of Paracetamol 1000mg Sustained-release Tablets in Patients With Osteoarthritis

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 3

Conditions: Pain

Treatments: Drug: Paracetamol 665 mg SR tablets; Drug: Paracetamol 1000 mg SR tablets; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02311881

202195

RH02448 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 960 patients

Sex: All

Ages: 40 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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960 participants in 3 patient groups, including a placebo group

Paracetamol 2000 mg twice daily (BID)

Experimental group

Description:

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.

Treatment:

Drug: Paracetamol 1000 mg SR tablets

Paracetamol 1330 mg thrice daily (TID)

Active Comparator group

Description:

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.

Treatment:

Drug: Paracetamol 665 mg SR tablets

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo