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

Pain Clinical Trial

Official title:

An Efficacy and Safety Study of Sustained-release Paracetamol in Subjects With Osteoarthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02311881
• Other study ID #: 202195
• Secondary ID: RH02448
• Status: Completed
• Phase: Phase 3
• First received: December 4, 2014
• Last updated: April 18, 2016
• Start date: January 2015
• Est. completion date: February 2016

Study information

• Verified date: April 2016
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1517
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteoarthritis
• Pain

Intervention

Drug:
• Paracetamol 1000 mg SR tablets
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 665 mg SR tablets
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.
• Placebo
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.

Locations

Country	Name	City	State
United States	GSK Investigational Site	Altoona	Pennsylvania
United States	GSK Investigational Site	Anaheim	California
United States	GSK Investigational Site	Bellevue	Nebraska
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Brandon	Florida
United States	GSK Investigational Site	Brooklyn	New York
United States	GSK Investigational Site	Buffalo	New York
United States	GSK Investigational Site	Carmichael	California
United States	GSK Investigational Site	Chandler	Arizona
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Clearwater	Florida
United States	GSK Investigational Site	Crestview Hills	Kentucky
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Dayton	Ohio
United States	GSK Investigational Site	Duncansville	Pennsylvania
United States	GSK Investigational Site	Edgewater	Florida
United States	GSK Investigational Site	Evanston	Illinois
United States	GSK Investigational Site	Fresno	California
United States	GSK Investigational Site	Hartsdale	New York
United States	GSK Investigational Site	Hialeah	Florida
United States	GSK Investigational Site	Hialeah	Florida
United States	GSK Investigational Site	Hickory	North Carolina
United States	GSK Investigational Site	Homestead	Florida
United States	GSK Investigational Site	Huntsville	Alabama
United States	GSK Investigational Site	Jupiter	Florida
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Mount Pleasant	South Carolina
United States	GSK Investigational Site	New Orleans	Louisiana
United States	GSK Investigational Site	North Hollywood	California
United States	GSK Investigational Site	Oklahoma	Oklahoma
United States	GSK Investigational Site	Oldsmar	Florida
United States	GSK Investigational Site	Omaha	Nebraska
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Oviedo	Florida
United States	GSK Investigational Site	Plano	Texas
United States	GSK Investigational Site	Port Orange	Florida
United States	GSK Investigational Site	Prairie Village	Kansas
United States	GSK Investigational Site	Saint Louis	Missouri
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	Savannah	Georgia
United States	GSK Investigational Site	Smithfield	Pennsylvania
United States	GSK Investigational Site	South Miami	Florida
United States	GSK Investigational Site	Toledo	Ohio
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Watertown	Massachusetts
United States	GSK Investigational Site	West Palm Beach	Florida
United States	GSK Investigational Site	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean change from baseline in Western Ontario McMaster (WOMAC) Pain over 12 weeks of treatment	Mean change from baseline for the 5-question WOMAC pain subscale will be measured periodically throughout the 12-week treatment period via 100mm visual analogue scale (VAS) where 0= never, 100= always. The mean changes of all time points will be summed together to determine the mean change from baseline over 12 weeks.	Over 12 weeks of treatment	No
Secondary	Mean change from baseline for WOMAC Pain subscales, WOMAC Stiffness subscale, WOMAC Physical Function, and WOMAC Total Index	The 5-question WOMAC Pain subscale, 2-question WOMAC Stiffness subscale, and 17-question WOMAC Function subscale will each be measured using independent 100mm VAS where 0= never, 100= always. The mean of each time point will be calculated separately for each subscale. The 24-question WOMAC Total Index will be derived by combining the values for each of the three WOMAC subscales. The mean of the 24-question WOMAC Total Index will be derived for each time point.	After 1, 2, 4, 8, and 12 weeks of treatment	No
Secondary	Mean change from baseline in Daily Pain, Daily Stiffness, and Daily Pain + Stiffness	Participants will assess their daily pain and stiffness each morning (upon awakening), afternoon, and evening during the 12-week treatment period using an independent 11-point Numerical Rating Scale (NRS), ranging from 0 (no pain) to 10 (extreme pain). The mean of pain, mean of stiffness, and summed mean of pain + stiffness (composite) will be calculated. Changes from baseline will be assessed periodically and over the entire 12-week treatment period.	Daily over 12 weeks of treatment	No
Secondary	Patient Global Assessment of Response to Therapy (PGART)	PGART will be accessed by a questionnaire using a 5-point categorical scale, ranging from 0 (None/No good at all/Ineffective) to 4 (Excellent/Ideal response/Virtually pain free). Mean PGART scores will be calculated periodically of the 12 week treatment period.	After 4, 8 and 12 weeks of treatment	No
Secondary	Mean change from baseline in Global Patient Assessment of Arthritis (GPAOA)	Participants will perform an instantaneous GPAOA via a 100mm VAS, ranging from 0 (best ever) to 100 (worst ever) periodically during the 12 week treatment period.	After 4, 8 and 12 weeks of treatment	No
Secondary	Responder rate (%)	The responder rate will be estimated improvement in response to therapy by combining the scores from the WOMAC Pain, WOMAC Physical Function, and PGART assessments over the 12-week treatment period for each participant. A participant will be considered a "responder" if his/her improvement satisfies at least one of the two criteria:- High improvement: mean change from baseline through week 12 that represents at least 50% decrease in WOMAC Pain or at least 60% decrease in WOMAC Physical Function. Moderate improvement: mean change from baseline through week 12 with fulfillment of at least two of the following criteria's: at least 30 % improvement in WOMAC Pain and/or at least 20% improvement in WOMAC Physical Function and/or; at least 25% improvement in GPAOA.	Over 12 weeks of treatment	No
Secondary	Mean Use of Rescue Medication	The mean number of doses of rescue medications taken throughout the 12-week treatment period will be calculated.	After 4, 8 and 12 weeks of treatment	No
Secondary	Mean change from baseline in Chronic Pain Sleep Inventory (CPSI)	Sleep Problem Index (SPI) will be calculated as mean of three CPSI questions: CPSI-1-'Trouble falling asleep': How often the participant had trouble falling asleep? , CPSI-2-'Awakening due to pain at night': How often the subject was awakened by pain during the night, CPSI-3-Awakening due to pain in the morning': How often the participant was awakened by pain in the morning? The participants will respond to these questions via 100mm VAS, ranging from 0 (never) to 100 (always).	After 4, 8 and 12 weeks of treatment	No
Secondary	Frequency of Adverse events (AEs)	AEs will be recorded for all participants who receive at least one dose of blinded study medication. The severity of AEs and their relationship to the blinded study medication will be coded using Medical Dictionary for Regulatory Activities (MedDRA) and summarized based on MedDRA system organ class and preferred terms. AE severity will be graded on a 3-point scale (Mild = Easily tolerated/Causing minimal discomfort and not interfering with normal everyday activities; Moderate = Sufficiently discomforting to interfere with normal everyday activities; Severe = Any event that prevents normal everyday activities).	Over 12 weeks of treatment	No
Secondary	Liver Function Testing	Liver function will be tested via biochemistry to determine the frequency of elevated liver enzymes.	After 1, 2, 4, 8 and 12 weeks of treatment	Yes