Trial Outcomes & Findings for A Study to Evaluate the Effect of Analgesics on a Walking Model of Knee Pain (0000-105)(COMPLETED) (NCT NCT00772967)

Last Updated: 2015-11-20

Results Overview

Baseline measurements of participant-specific knee PI were gathered pre-dose on Day 1 from the briskest possible self-pace constant walks on a treadmill over the course of a 20 minute interval. Over this interval PI readings were taken at time points 0,3,6,9,12,15,18 and 20 minutes, rated on an 11-point numeric rating scale (NRS), with 0: No Pain - 10: Worst Pain You Can Imagine. Following a single treatment on Day 3, PI was similarly measured over 20 minute self paced walks at 4 and 6 hrs post-dose. The difference between the TWA (0-20 minutes) PI determined at baseline, and the average of the two TWA (0-20 minutes) PI from the self-paced walks on Day 3 is reported as units on a scale.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

22 participants

Primary outcome timeframe

Baseline and Day 3

Results posted on

2015-11-20

Participant Flow

First Patient Entered: 23 June 2008 Last Patient, Last Visit: 20 November 2008 2 sites

Inclusion criteria: Patient has osteoarthritis of the knee and primary source of pain is knee Titration schedule for Ultracet® (Acetaminophen 325 mg and tramadol hydrochloride 37.5 mg): twice on Day 1, three times on Day 2, and twice on the morning of Day 3. Naproxen tablets 500 mg twice daily on Days 1 and 2 and 500 mg once daily on Day 3.

Participant milestones

Participant milestones
Measure	Placebo, Naproxen, Ultracet Placebo in Treatment Period 1, Naproxen in Treatment Period 2, Ultracet in Treatment Period 3.	Naproxen, Ultracet, Placebo Naproxen in Treatment Period 1, Ultracet in Treatment Period 2, Placebo in Treatment Period 3.	Ultracet, Placebo, Naproxen Ultracet in Treatment Period 1, Placebo in Treatment Period 2, Naproxen in Treatment Period 3.	Placebo, Ultracet, Naproxen Placebo in Treatment Period 1, Ultracet in Treatment Period 2, Naproxen in Treatment Period 3.	Naproxen, Placebo, Ultracet Naproxen in Treatment Period 1, Placebo in Treatment Period 2, Ultracet inTreatment Period 3.	Ultracet, Naproxen, Placebo Ultracet in Treatment Period 1, Naproxen in Treatment Period 2, Placebo in Treatment Period 3.
Crossover Treatment 1 STARTED	3	5	3	4	4	3
Crossover Treatment 1 COMPLETED	3	5	3	3	4	3
Crossover Treatment 1 NOT COMPLETED	0	0	0	1	0	0
Break 1 (4-7 Days) STARTED	3	5	3	3	4	3
Break 1 (4-7 Days) COMPLETED	3	4	3	3	4	3
Break 1 (4-7 Days) NOT COMPLETED	0	1	0	0	0	0
Crossover Treatment 2 STARTED	3	4	3	3	4	3
Crossover Treatment 2 COMPLETED	3	4	3	3	4	3
Crossover Treatment 2 NOT COMPLETED	0	0	0	0	0	0
Break 2 (4-7 Days) STARTED	3	4	3	3	4	3
Break 2 (4-7 Days) COMPLETED	3	4	3	3	4	3
Break 2 (4-7 Days) NOT COMPLETED	0	0	0	0	0	0
Crossover Treatment 3 STARTED	3	4	3	3	4	3
Crossover Treatment 3 COMPLETED	3	4	3	3	3	3
Crossover Treatment 3 NOT COMPLETED	0	0	0	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Naproxen, Ultracet, Placebo Naproxen in Treatment Period 1, Ultracet in Treatment Period 2, Placebo in Treatment Period 3.	Placebo, Ultracet, Naproxen Placebo in Treatment Period 1, Ultracet in Treatment Period 2, Naproxen in Treatment Period 3.	Naproxen, Placebo, Ultracet Naproxen in Treatment Period 1, Placebo in Treatment Period 2, Ultracet inTreatment Period 3.
Crossover Treatment 1 Adverse Event (Pain)	0	1	0
Break 1 (4-7 Days) Withdrawal by Subject	1	0	0
Crossover Treatment 3 Adverse Event	0	0	1

Baseline Characteristics

A Study to Evaluate the Effect of Analgesics on a Walking Model of Knee Pain (0000-105)(COMPLETED)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=22 Participants All randomized participants
Age, Continuous	59.6 Years STANDARD_DEVIATION 7.92 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 3

Population: All treated participants who provided baseline and at least one on-treatment observation

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Participants treated with at least one dose of Placebo	Naproxen n=21 Participants Participants treated with at least one dose of Naproxen	Ultracet n=19 Participants Participants treated with at least one dose of Ultracet.
Change From Baseline in Time Weighted Average (TWA) Pain Intensity (PI) on a Numeric Rating Scale (NRS) Due to Self-paced Walks on Day 3	-0.927 units on a scale Interval -1.52 to -0.33	-1.54 units on a scale Interval -2.12 to -0.96	-1.73 units on a scale Interval -2.34 to -1.12

SECONDARY outcome

Timeframe: Baseline and Day 1

Population: All treated participants who provided baseline and at least one on-treatment observation

Baseline measurements of participant-specific knee PI were gathered pre-dose on Day 1 from the briskest possible self-pace constant walks on a treadmill over the course of a 20 minute interval. Over this interval PI readings were taken at time points 0,3,6,9,12,15,18 and 20 minutes, rated on an 11-point numeric rating scale (NRS), with 0: No Pain - 10: Worst Pain You Can Imagine. Following the first treatment on Day 1, PI was similarly measured over 20 minute self-paced walks at 2, 4, and 6 hrs post-dose . The difference between the TWA (0-20 minutes) PI determined at baseline, and the average of the three TWA (0-20 minutes)PI from the self-paced walks on Day 1 is reported as units on a scale.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants treated with at least one dose of Placebo	Naproxen n=21 Participants Participants treated with at least one dose of Naproxen	Ultracet n=21 Participants Participants treated with at least one dose of Ultracet.
Change From Baseline in Time Weighted Average (TWA) Pain Intensity (PI) on a Numeric Rating Scale (NRS) Due to Self-paced Walks on Day 1	-0.438 units on a scale Interval -0.98 to 0.11	-0.956 units on a scale Interval -1.51 to -0.4	-1.47 units on a scale Interval -2.02 to -0.92

SECONDARY outcome

Timeframe: Baseline and Day 1

Population: All treated participants who provided baseline and at least one on-treatment observation

Baseline measurements of participant-specific knee PI were gathered pre-dose on Day 1 from the briskest possible self-pace constant walks on a treadmill over the course of a 20 minute interval. Over this interval PI readings were taken at time points 0,3,6,9,12,15,18 and 20 minutes,rated on an 11-point numeric rating scale (NRS), with 0: No Pain - 10: Worst Pain You Can Imagine. Following the first treatment on Day 1, PI was similarly measured over a 20 minute high-paced treadmill walk at 5 hrs post-dose. A high-paced walk is the highest pace that can be walked safely for at least 5 minutes that is at a 10-30% higher rate than a self-paced walk. The difference between the TWA (0-20 minutes) PI determined at baseline, and the TWA (0-20 minutes) PI of the high-paced walk on Day 1 is reported as units on a scale.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants treated with at least one dose of Placebo	Naproxen n=21 Participants Participants treated with at least one dose of Naproxen	Ultracet n=21 Participants Participants treated with at least one dose of Ultracet.
Change From Baseline in Time Weighted Average (TWA) Pain Intensity (PI) on a Numeric Rating Scale (NRS) Due to High-paced Walks on Day 1	0.150 units on a scale Interval -0.52 to 0.82	-0.508 units on a scale Interval -1.18 to 0.17	-1.00 units on a scale Interval -1.67 to -0.34

SECONDARY outcome

Timeframe: Baseline and Day 3

Population: All treated participants who provided baseline and at least one on-treatment observation

Baseline measurements of participant-specific knee PI were gathered pre-dose on Day 1 from the briskest possible self-pace constant walks on a treadmill over the course of a 20 minute interval. Over this interval PI readings were taken at time points 0,3,6,9,12,15,18 and 20 minutes, rated on an 11-point numeric rating scale (NRS), with 0: No Pain - 10: Worst Pain You Can Imagine. Following a single treatment on Day 3, PI was similarly measured over a 20 minute high-paced treadmill walk, at 5 hrs post-dose. A high-paced walk is the highest pace that can be walked safely for at least 5 minutes that is at a 10-30% higher rate than a self-paced walk. The difference between the TWA (0-20 minutes) PI determined at baseline, and the TWA (0-20 minutes) PI of the high-paced walk on Day 3 is reported as units on a scale.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Participants treated with at least one dose of Placebo	Naproxen n=21 Participants Participants treated with at least one dose of Naproxen	Ultracet n=19 Participants Participants treated with at least one dose of Ultracet.
Change From Baseline in Time Weighted Average (TWA) Pain Intensity (PI) on a Numeric Rating Scale (NRS) Due to High-paced Walks on Day 3	-0.234 units on a scale Interval -0.85 to 0.38	-1.11 units on a scale Interval -1.71 to -0.51	-1.30 units on a scale Interval -1.93 to -0.67

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Naproxen

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Ultracet

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo n=22 participants at risk Participants treated with at least one dose of Placebo	Naproxen n=22 participants at risk Participants treated with at least one dose of Naproxen	Ultracet n=20 participants at risk Participants treated with at least one dose of Ultracet. Two participants were not treated due to discontinuation.
Metabolism and nutrition disorders Gout	0.00% 0/22 • Adverse experiences (AEs) were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AEs were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Patients were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/22 • Adverse experiences (AEs) were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AEs were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Patients were queried at each visit for any adverse experiences since the previous visit.	5.0% 1/20 • Adverse experiences (AEs) were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AEs were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Patients were queried at each visit for any adverse experiences since the previous visit.
Nervous system disorders Somnolence	0.00% 0/22 • Adverse experiences (AEs) were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AEs were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Patients were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/22 • Adverse experiences (AEs) were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AEs were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Patients were queried at each visit for any adverse experiences since the previous visit.	5.0% 1/20 • Adverse experiences (AEs) were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AEs were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Patients were queried at each visit for any adverse experiences since the previous visit.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER