A Pilot Study Assessing the Treatment Responsiveness of a Novel Osteoarthritis Stiffness Scale

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03570554
• Collaborator: (none)
• Enrollment: 41
• Locations: 5
• Arms: 4
• Actual Duration (Months): 11.5
• Patients Per Site: 8.2
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

Osteoarthritis is a common, chronic, progressive, skeletal, degenerative disorder that frequently affects several joints such as knee, hip, spine and hands.This placebo-controlled clinical trial assessed the effects of naproxen sodium, acetaminophen and celecoxib on stiffness in subjects with osteoarthritis.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis, Knee	Drug: Naproxen Sodium (Aleve, BAY117031); Drug: Acetaminophen ER; Drug: Celecoxib; Drug: Placebo	Phase 2

Detailed Description

The primary objective of the study was to assess the responsiveness of the Brief Arthritis Stiffness Scale (BASS) for detecting treatment effects of common over-the-counter (OTC) analgesics and a common prescription analgesic in subjects with knee osteoarthritis.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Pilot Study Assessing the Treatment Responsiveness of a Novel Osteoarthritis Stiffness Scale
• Actual Study Start Date: Jun 29, 2018
• Actual Primary Completion Date: Jun 14, 2019
• Actual Study Completion Date: Jun 14, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment A-D-C-B Participants received naproxen 660 mg daily for 3 days and 440 mg on the fourth day; followed by placebo for 4 days; followed by celecoxib 200 mg daily for 3 days and 100 mg on the fourth day; followed by acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day. Treatment periods were separated by a washout period of 3 to 7 days.	Drug: Naproxen Sodium (Aleve, BAY117031); 660 mg daily for 3 days, 440 mg on the fourth day, over-encapsulated tablet, oral (Treatment A); Drug: Acetaminophen ER; 3900 mg daily for 3 days, 1300 mg on the fourth day, over-encapsulated extended release (ER) tablet, oral (Treatment B); Drug: Celecoxib; 200 mg daily for 3 days, 100 mg on the fourth day, over-encapsulated capsule, oral (Treatment C); Drug: Placebo; Over-encapsulation capsule, 4 days, oral (Treatment D)
Experimental: Treatment B-C-D-A Participants received acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day; followed by celecoxib 200 mg daily for 3 days and 100 mg on the fourth day; followed by placebo for 4 days; followed by naproxen 660 mg daily for 3 days and 440 mg on the fourth day. Treatment periods were separated by a washout period of 3 to 7 days.	Drug: Naproxen Sodium (Aleve, BAY117031); 660 mg daily for 3 days, 440 mg on the fourth day, over-encapsulated tablet, oral (Treatment A); Drug: Acetaminophen ER; 3900 mg daily for 3 days, 1300 mg on the fourth day, over-encapsulated extended release (ER) tablet, oral (Treatment B); Drug: Celecoxib; 200 mg daily for 3 days, 100 mg on the fourth day, over-encapsulated capsule, oral (Treatment C); Drug: Placebo; Over-encapsulation capsule, 4 days, oral (Treatment D)
Experimental: Treatment C-A-B-D Participants received celecoxib 200 mg daily for 3 days and 100 mg on the fourth day; followed by naproxen 660 mg daily for 3 days and 440 mg on the fourth day; followed by acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day; followed by placebo for 4 days. Treatment periods were separated by a washout period of 3 to 7 days.	Drug: Naproxen Sodium (Aleve, BAY117031); 660 mg daily for 3 days, 440 mg on the fourth day, over-encapsulated tablet, oral (Treatment A); Drug: Acetaminophen ER; 3900 mg daily for 3 days, 1300 mg on the fourth day, over-encapsulated extended release (ER) tablet, oral (Treatment B); Drug: Celecoxib; 200 mg daily for 3 days, 100 mg on the fourth day, over-encapsulated capsule, oral (Treatment C); Drug: Placebo; Over-encapsulation capsule, 4 days, oral (Treatment D)
Experimental: Treatment D-B-A-C Participants received placebo for 4 days; followed by acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day; followed by naproxen 660 mg daily for 3 days and 440 mg on the fourth day; followed by celecoxib 200 mg daily for 3 days and 100 mg on the fourth day. Treatment periods were separated by a washout period of 3 to 7 days	Drug: Naproxen Sodium (Aleve, BAY117031); 660 mg daily for 3 days, 440 mg on the fourth day, over-encapsulated tablet, oral (Treatment A); Drug: Acetaminophen ER; 3900 mg daily for 3 days, 1300 mg on the fourth day, over-encapsulated extended release (ER) tablet, oral (Treatment B); Drug: Celecoxib; 200 mg daily for 3 days, 100 mg on the fourth day, over-encapsulated capsule, oral (Treatment C); Drug: Placebo; Over-encapsulation capsule, 4 days, oral (Treatment D)

Outcome Measures

Primary Outcome Measures

1. Sum of Change in Brief Arthritis Stiffness Scale (BASS) Scores Over the 4-day Treatment Period [4 days]

   Brief Arthritis Stiffness Scale (BASS) is a patient-reported outcome (PRO) instrument measuring of the severity of osteoarthritis-related stiffness in the target knee joint. The BASS score ranges from 0 to 40 and a higher score indicates worse stiffness. This endpoint was calculated by summing the changes from baseline (CFB) in BASS scores at Days 2, 3, and 4 of the treatment periods.

Secondary Outcome Measures

1. Absolute Brief Arthritis Stiffness Scale (BASS) Score at Each Time Point [4 days]

   Brief Arthritis Stiffness Scale (BASS) is a patient-reported outcome (PRO) instrument measuring of the severity of osteoarthritis-related stiffness in the target knee joint. The BASS score ranges from 0 to 40 and a higher score indicates worse stiffness.

2. Change From Baseline in Brief Arthritis Stiffness Scale (BASS) Score at Day 4 [Day 4]

   Brief Arthritis Stiffness Scale (BASS) is a patient-reported outcome (PRO) instrument measuring of the severity of osteoarthritis-related stiffness in the target knee joint. The BASS score ranges from 0 to 40 and a higher score indicates worse stiffness.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age between 40 and 80 years

• Body Mass Index (BMI) between 18 and <40 kg/m^2

• Unilateral or bilateral osteoarthritis of the knee

• Diagnostic quality radiography of the target knee performed no more than 1 year prior to baseline showing evidence of osteoarthritis (OA) with Kellgren and Lawrence grade of II or III

• Joint Stiffness Severity score ≥3.0 on a 0-10 numerical rating scale (NRS) at screening

Exclusion Criteria:

• History of underlying inflammatory arthropathy, rheumatoid arthritis or fibromyalgia

• History of or scheduled for target knee replacement surgery

• Recent injury in target knee (past 4 months)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Radiant Research, Inc.	Chandler	Arizona	United States	85224
2	Radiant Research, Inc.	Pinellas Park	Florida	United States	33781
3	Radiant Research, Inc.	Chicago	Illinois	United States	60602
4	Radiant Research, Inc.	Cincinnati	Ohio	United States	45236
5	Radiant Research, Inc.	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• Bayer

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Sep 11, 2018
• Statistical Analysis Plan - Sep 25, 2019

More Information

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT03570554
• Other Study ID Numbers: 19783
• First Posted: Jun 27, 2018
• Last Update Posted: Jun 19, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Knee; Acetaminophen; Celecoxib; Naproxen

Study Results

Participant Flow

Recruitment Details	Study was conducted at multiple centers in the US between 29 June 2018 (first participant first visit) and 14 June 2019 (last participant last visit).
Pre-assignment Detail	Overall, 209 participants were screened. Of them, 168 participants were screen failures, and 41 subjects were randomized to study treatments.

Arm/Group Title	Treatment A-D-C-B	Treatment B-C-D-A	Treatment C-A-B-D	Treatment D-B-A-C
Arm/Group Description	Participants received naproxen 660 mg daily for 3 days and 440 mg on the fourth day; followed by placebo for 4 days; followed by celecoxib 200 mg daily for 3 days and 100 mg on the fourth day; followed by acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day. Treatment periods were separated by a washout period of 3 to 7 days.	Participants received acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day; followed by celecoxib 200 mg daily for 3 days and 100 mg on the fourth day; followed by placebo for 4 days; followed by naproxen 660 mg daily for 3 days and 440 mg on the fourth day. Treatment periods were separated by a washout period of 3 to 7 days.	Participants received celecoxib 200 mg daily for 3 days and 100 mg on the fourth day; followed by naproxen 660 mg daily for 3 days and 440 mg on the fourth day; followed by acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day; followed by placebo for 4 days. Treatment periods were separated by a washout period of 3 to 7 days.	Participants received placebo for 4 days; followed by acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day; followed by naproxen 660 mg daily for 3 days and 440 mg on the fourth day; followed by celecoxib 200 mg daily for 3 days and 100 mg on the fourth day. Treatment periods were separated by a washout period of 3 to 7 days.
Period Title: Overall Study
STARTED	10	10	11	10
COMPLETED	10	10	10	9
NOT COMPLETED	0	0	1	1

Baseline Characteristics

Arm/Group Title	Treatment A-D-C-B	Treatment B-C-D-A	Treatment C-A-B-D	Treatment D-B-A-C	Total
Arm/Group Description	Participants received naproxen 660 mg daily for 3 days and 440 mg on the fourth day; followed by placebo for 4 days; followed by celecoxib 200 mg daily for 3 days and 100 mg on the fourth day; followed by acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day. Treatment periods were separated by a washout period of 3 to 7 days.	Participants received acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day; followed by celecoxib 200 mg daily for 3 days and 100 mg on the fourth day; followed by placebo for 4 days; followed by naproxen 660 mg daily for 3 days and 440 mg on the fourth day. Treatment periods were separated by a washout period of 3 to 7 days.	Participants received celecoxib 200 mg daily for 3 days and 100 mg on the fourth day; followed by naproxen 660 mg daily for 3 days and 440 mg on the fourth day; followed by acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day; followed by placebo for 4 days. Treatment periods were separated by a washout period of 3 to 7 days.	Participants received placebo for 4 days; followed by acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day; followed by naproxen 660 mg daily for 3 days and 440 mg on the fourth day; followed by celecoxib 200 mg daily for 3 days and 100 mg on the fourth day. Treatment periods were separated by a washout period of 3 to 7 days.	Total of all reporting groups
Overall Participants	10	10	11	10	41
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62.4 (9.20)	61.3 (8.77)	61.6 (7.55)	59.6 (8.28)	61.2 (8.19)
Sex: Female, Male (Count of Participants)
Female	9 90%	6 60%	11 100%	7 70%	33 80.5%
Male	1 10%	4 40%	0 0%	3 30%	8 19.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 10%	0 0%	2 18.2%	1 10%	4 9.8%
Not Hispanic or Latino	9 90%	10 100%	9 81.8%	9 90%	37 90.2%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	1 9.1%	0 0%	1 2.4%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	4 40%	5 50%	2 18.2%	5 50%	16 39%
White	6 60%	5 50%	8 72.7%	5 50%	24 58.5%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Brief Arthritis Stiffness Scale (BASS) (Scores on a scale) [Mean (Standard Deviation) ]
Treatment period 1	26.7 (4.90)	25.8 (5.05)	27.8 (5.56)	23.1 (5.35)	26.0 (5.31)
Treatment period 2	25.8 (7.74)	21.8 (8.32)	22.3 (9.74)	25.3 (4.64)	23.8 (7.74)
Treatment period 3	26.3 (5.56)	17.7 (10.03)	22.9 (10.29)	24.0 (6.48)	22.7 (8.69)
Treatment period 4	21.9 (10.56)	20.3 (6.40)	24.2 (9.95)	23.8 (7.92)	22.5 (8.68)

Outcome Measures

1. Primary Outcome

Title	Sum of Change in Brief Arthritis Stiffness Scale (BASS) Scores Over the 4-day Treatment Period
Description	Brief Arthritis Stiffness Scale (BASS) is a patient-reported outcome (PRO) instrument measuring of the severity of osteoarthritis-related stiffness in the target knee joint. The BASS score ranges from 0 to 40 and a higher score indicates worse stiffness. This endpoint was calculated by summing the changes from baseline (CFB) in BASS scores at Days 2, 3, and 4 of the treatment periods.
Time Frame	4 days

Outcome Measure Data

Analysis Population Description

Per-protocol (PP) population: all subjects who were randomly assigned and had taken at least one dose of IMP without major protocol violations that could affect the evaluability of the primary efficacy parameter.

Arm/Group Title	Naproxen	Acetaminophen ER	Celecoxib	Placebo
Arm/Group Description	Participants received naproxen 660 mg daily for 3 days and 440 mg on the fourth day.	Participants received acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day.	Participants received celecoxib 200 mg daily for 3 days and 100 mg on the fourth day.	Participants received placebo for 4 days.
Measure Participants	37	37	37	36
Least Squares Mean (Standard Error) [Scores on a scale]	-12.6 (5.46)	-13.6 (5.46)	-11.7 (5.46)	-2.3 (5.47)

2. Secondary Outcome

Title	Absolute Brief Arthritis Stiffness Scale (BASS) Score at Each Time Point
Description	Brief Arthritis Stiffness Scale (BASS) is a patient-reported outcome (PRO) instrument measuring of the severity of osteoarthritis-related stiffness in the target knee joint. The BASS score ranges from 0 to 40 and a higher score indicates worse stiffness.
Time Frame	4 days

Outcome Measure Data

Analysis Population Description

Per-protocol (PP) population: all subjects who were randomly assigned and had taken at least one dose of IMP without major protocol violations that could affect the evaluability of the primary efficacy parameter.

Arm/Group Title	Naproxen	Acetaminophen ER	Celecoxib	Placebo
Arm/Group Description	Participants received naproxen 660 mg daily for 3 days and 440 mg on the fourth day.	Participants received acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day.	Participants received celecoxib 200 mg daily for 3 days and 100 mg on the fourth day.	Participants received placebo for 4 days.
Measure Participants	37	37	37	36
Day 1	23.0 (1.84)	23.3 (1.84)	24.6 (1.84)	22.6 (1.85)
Day 2	20.8 (1.62)	19.7 (1.62)	20.6 (1.62)	23.2 (1.62)
Day 3	18.4 (1.97)	18.4 (1.97)	18.9 (1.98)	22.4 (1.98)
Day 4	18.1 (1.97)	18.0 (1.97)	18.5 (1.97)	22.0 (1.97)

3. Secondary Outcome

Title	Change From Baseline in Brief Arthritis Stiffness Scale (BASS) Score at Day 4
Description	Brief Arthritis Stiffness Scale (BASS) is a patient-reported outcome (PRO) instrument measuring of the severity of osteoarthritis-related stiffness in the target knee joint. The BASS score ranges from 0 to 40 and a higher score indicates worse stiffness.
Time Frame	Day 4

Outcome Measure Data

Analysis Population Description

Per-protocol (PP) population: All subjects who were randomly assigned and had taken at least one dose of IMP without major protocol violations that could affect the evaluability of the primary efficacy parameter.

Arm/Group Title	Naproxen	Acetaminophen ER	Celecoxib	Placebo
Arm/Group Description	Participants received naproxen 660 mg daily for 3 days and 440 mg on the fourth day.	Participants received acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day.	Participants received celecoxib 200 mg daily for 3 days and 100 mg on the fourth day.	Participants received placebo for 4 days.
Measure Participants	37	37	37	36
Least Squares Mean (Standard Error) [Scores on a scale]	-5.2 (1.97)	-5.3 (1.97)	-4.8 (1.97)	-1.3 (1.97)

Adverse Events

Time Frame	After the first dose of the investigational medicinal product (IMP) until the end of the treatment phase, up to 37 days
Arm/Group Title	Naproxen		Acetaminophen ER		Celecoxib		Placebo
Arm/Group Description	Participants received naproxen 660 mg daily for 3 days and 440 mg on the fourth day		Participants received acetaminophen 3900 mg daily for 3 days and 1300 mg on the fourth day		Participants received celecoxib 200 mg daily for 3 days and 100 mg on the fourth day		Participants received placebo for 4 days
All Cause Mortality
	Naproxen		Acetaminophen ER		Celecoxib		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		0/40 (0%)		0/40 (0%)		0/39 (0%)
Serious Adverse Events
	Naproxen		Acetaminophen ER		Celecoxib		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		0/40 (0%)		0/40 (0%)		0/39 (0%)
Other (Not Including Serious) Adverse Events
	Naproxen		Acetaminophen ER		Celecoxib		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/39 (12.8%)		8/40 (20%)		10/40 (25%)		3/39 (7.7%)
Ear and labyrinth disorders
Cerumen impaction	0/39 (0%)	0	1/40 (2.5%)	1	0/40 (0%)	0	0/39 (0%)	0
Gastrointestinal disorders
Vomiting	0/39 (0%)	0	2/40 (5%)	2	0/40 (0%)	0	0/39 (0%)	0
Abdominal discomfort	0/39 (0%)	0	0/40 (0%)	0	1/40 (2.5%)	1	0/39 (0%)	0
Abdominal distension	1/39 (2.6%)	1	0/40 (0%)	0	0/40 (0%)	0	0/39 (0%)	0
Abdominal pain	1/39 (2.6%)	1	0/40 (0%)	0	0/40 (0%)	0	0/39 (0%)	0
Diarrhoea	0/39 (0%)	0	0/40 (0%)	0	0/40 (0%)	0	1/39 (2.6%)	1
Dry mouth	1/39 (2.6%)	1	0/40 (0%)	0	0/40 (0%)	0	0/39 (0%)	0
Dyspepsia	0/39 (0%)	0	0/40 (0%)	0	1/40 (2.5%)	1	0/39 (0%)	0
Faeces discoloured	1/39 (2.6%)	1	0/40 (0%)	0	0/40 (0%)	0	0/39 (0%)	0
General disorders
Chills	0/39 (0%)	0	1/40 (2.5%)	1	0/40 (0%)	0	0/39 (0%)	0
Fatigue	0/39 (0%)	0	0/40 (0%)	0	1/40 (2.5%)	1	0/39 (0%)	0
Infections and infestations
Oral herpes	0/39 (0%)	0	0/40 (0%)	0	1/40 (2.5%)	1	0/39 (0%)	0
Pharyngitis streptococcal	0/39 (0%)	0	0/40 (0%)	0	1/40 (2.5%)	1	0/39 (0%)	0
Upper respiratory tract infection	0/39 (0%)	0	0/40 (0%)	0	1/40 (2.5%)	1	1/39 (2.6%)	1
Injury, poisoning and procedural complications
Joint injury	1/39 (2.6%)	1	0/40 (0%)	0	0/40 (0%)	0	0/39 (0%)	0
Limb injury	0/39 (0%)	0	1/40 (2.5%)	1	0/40 (0%)	0	0/39 (0%)	0
Investigations
Heart rate decreased	1/39 (2.6%)	1	0/40 (0%)	0	0/40 (0%)	0	0/39 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/39 (0%)	0	1/40 (2.5%)	1	0/40 (0%)	0	0/39 (0%)	0
Nervous system disorders
Dizziness	0/39 (0%)	0	0/40 (0%)	0	1/40 (2.5%)	1	0/39 (0%)	0
Headache	1/39 (2.6%)	1	1/40 (2.5%)	1	1/40 (2.5%)	1	1/39 (2.6%)	1
Neuropathy peripheral	0/39 (0%)	0	0/40 (0%)	0	0/40 (0%)	0	1/39 (2.6%)	1
Somnolence	0/39 (0%)	0	0/40 (0%)	0	1/40 (2.5%)	1	0/39 (0%)	0
Tension headache	1/39 (2.6%)	1	0/40 (0%)	0	0/40 (0%)	0	0/39 (0%)	0
Psychiatric disorders
Insomnia	1/39 (2.6%)	1	0/40 (0%)	0	0/40 (0%)	0	0/39 (0%)	0
Sleep disorder	0/39 (0%)	0	1/40 (2.5%)	1	0/40 (0%)	0	0/39 (0%)	0
Renal and urinary disorders
Pollakiuria	0/39 (0%)	0	0/40 (0%)	0	0/40 (0%)	0	1/39 (2.6%)	1
Respiratory, thoracic and mediastinal disorders
Cough	0/39 (0%)	0	1/40 (2.5%)	1	0/40 (0%)	0	0/39 (0%)	0
Oropharyngeal pain	1/39 (2.6%)	1	0/40 (0%)	0	0/40 (0%)	0	0/39 (0%)	0
Skin and subcutaneous tissue disorders
Rash	0/39 (0%)	0	0/40 (0%)	0	1/40 (2.5%)	1	0/39 (0%)	0
Vascular disorders
Hypertension	0/39 (0%)	0	0/40 (0%)	0	1/40 (2.5%)	1	0/39 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.