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

NCT02311881 | Completed Phase 3 Results

• 2 other identifiers: 202195RH02448
• Study Type: interventional
• Target: 960
• Locations: 1 country
• Sites: 56

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.

Conditions

Pain

Outcome Measures

Primary Outcomes (1)

• Time-weighted Mean Change From Baseline in Western Ontario McMaster (WOMAC) Pain Through Week 12 of Treatment

  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).

  Baseline up to week 12

Secondary Outcomes (9)

• 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

Study Arms (3)

Paracetamol 2000 mg twice daily (BID)

EXPERIMENTAL

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.

Drug: Paracetamol 1000 mg SR tablets

Paracetamol 1330 mg thrice daily (TID)

ACTIVE COMPARATOR

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.

Drug: Paracetamol 665 mg SR tablets

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Paracetamol 1000 mg SR tablets DRUG

Two paracetamol 1000 mg SR tablets administered orally two times a day plus two placebo-matched paracetamol 665 mg SR tablets administered orally three times a day for 12 weeks.

Paracetamol 2000 mg twice daily (BID)

Paracetamol 665 mg SR tablets DRUG

Two paracetamol 665 mg SR tablets administered orally three times a day plus two placebo-matched paracetamol 1000 mg SR tablets administered orally two times a day for 12 weeks.

Paracetamol 1330 mg thrice daily (TID)

Placebo DRUG

Two placebo-matched paracetamol 665 mg SR tablets administered orally three times a day plus two placebo-matched paracetamol 1000 mg SR tablets administered orally two times a day for 12 weeks.

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (56)

GSK Investigational Site

Birmingham, Alabama, 35242, United States

Location

GSK Investigational Site

Huntsville, Alabama, 35801, United States

Location

GSK Investigational Site

Chandler, Arizona, 85224, United States

Location

GSK Investigational Site

Tucson, Arizona, 85712, United States

Location

GSK Investigational Site

Tucson, Arizona, 85745, United States

Location

GSK Investigational Site

Anaheim, California, 92801, United States

Location

GSK Investigational Site

Carmichael, California, 95608, United States

Location

GSK Investigational Site

Fresno, California, 93702, United States

Location

GSK Investigational Site

North Hollywood, California, 91606-1559, United States

Location

GSK Investigational Site

San Diego, California, 92103, United States

Location

GSK Investigational Site

Brandon, Florida, 33511, United States

Location

GSK Investigational Site

Clearwater, Florida, 33756, United States

Location

GSK Investigational Site

Edgewater, Florida, 32132, United States

Location

GSK Investigational Site

Hialeah, Florida, 33012, United States

Location

GSK Investigational Site

Hialeah, Florida, 33016, United States

Location

GSK Investigational Site

Homestead, Florida, 33030, United States

Location

GSK Investigational Site

Jupiter, Florida, 33458, United States

Location

GSK Investigational Site

Miami, Florida, 33155, United States

Location

GSK Investigational Site

Miami, Florida, 33173, United States

Location

GSK Investigational Site

Miami, Florida, 33185, United States

Location

GSK Investigational Site

Oldsmar, Florida, 34677, United States

Location

GSK Investigational Site

Orlando, Florida, 32806, United States

Location

GSK Investigational Site

Oviedo, Florida, 32765, United States

Location

GSK Investigational Site

Port Orange, Florida, 32127, United States

Location

GSK Investigational Site

South Miami, Florida, 33143, United States

Location

GSK Investigational Site

West Palm Beach, Florida, 33409, United States

Location

GSK Investigational Site

Savannah, Georgia, 31406, United States

Location

GSK Investigational Site

Chicago, Illinois, 60640, United States

Location

GSK Investigational Site

Evanston, Illinois, 60201, United States

Location

GSK Investigational Site

Prairie Village, Kansas, 66206, United States

Location

GSK Investigational Site

Wichita, Kansas, 67203, United States

Location

GSK Investigational Site

Crestview Hills, Kentucky, 41017, United States

Location

GSK Investigational Site

New Orleans, Louisiana, 70115, United States

Location

GSK Investigational Site

Watertown, Massachusetts, 02472, United States

Location

GSK Investigational Site

St Louis, Missouri, 63139, United States

Location

GSK Investigational Site

Bellevue, Nebraska, 68005, United States

Location

GSK Investigational Site

Omaha, Nebraska, 68134, United States

Location

GSK Investigational Site

Las Vegas, Nevada, 89119, United States

Location

GSK Investigational Site

Brooklyn, New York, 11230, United States

Location

GSK Investigational Site

Buffalo, New York, 14223, United States

Location

GSK Investigational Site

Hartsdale, New York, United States

Location

GSK Investigational Site

Hickory, North Carolina, 28601, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45227, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45242, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45255, United States

Location

GSK Investigational Site

Dayton, Ohio, 45424, United States

Location

GSK Investigational Site

Toledo, Ohio, 43623, United States

Location

GSK Investigational Site

Oklahoma City, Oklahoma, 73119, United States

Location

GSK Investigational Site

Altoona, Pennsylvania, 16602, United States

Location

GSK Investigational Site

Duncansville, Pennsylvania, 16635, United States

Location

GSK Investigational Site

Smithfield, Pennsylvania, 15478, United States

Location

GSK Investigational Site

Mt. Pleasant, South Carolina, 29464, United States

Location

GSK Investigational Site

Dallas, Texas, 75230, United States

Location

GSK Investigational Site

Plano, Texas, 75075, United States

Location

GSK Investigational Site

San Antonio, Texas, 78209, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Pain

Interventions

Acetaminophen

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2014
• First Posted: December 9, 2014
• Study Start: January 1, 2015
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: April 7, 2017
• Results First Posted: April 7, 2017

Record last verified: 2017-02

Locations

US (56)