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

A Phase 1 study testing Naproxen and Ultracet in people with Osteoarthritis, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

This study will evaluate a walking model of osteoarthritis for use in testing of new therapeutic agents. The primary hypothesis is that participants treated with Naproxen or Ultracet will have lower Pain Intensity (PI) than those treated with Placebo during self-paced walks on Day 3 of treatment. Read more about this study

Who is it for?: Ages 45 years and older
Conditions the study is for: Osteoarthritis
What is being tested?: Naproxen and Ultracet
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 22 participants
Where: No sites listed yet
Study dates: Jun 2008to Nov 2008
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 45 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Has osteoarthritis of the knee and primary source of pain is knee
Females must not be pregnant or nursing and must agree to use birth control throughout the study
Is willing to limit alcohol and caffeine intake
Is willing to abstain from smoking during study visits
Must be able to walk on a treadmill at a pace of at least 1 mile/hour

Who cannot join

Has a medical/arthritic disease that would interfere with evaluation
Is unable to take naproxen or Ultracet
Has congestive heart failure or angina
Has a history of stroke
Has a history of uncontrolled high blood pressure
Has a history of cancer
Regularly uses a walker or cane

About this study

Official title: A Double-Blind, Placebo-Controlled, 3-Period Crossover Study to Evaluate the Analgesic Effects of Naproxen and Ultracet in a Walking Model of Osteoarthritis Knee Pain

Conditions: Osteoarthritis
Being tested: Naproxen, Placebo, Ultracet
Medical subject headings: Osteoarthritis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NaproxenDrug
Naproxen tablets 500 mg twice daily on Day 1, a first dose at t = 0 hrs, and a second dose at t = 12 hrs. Twice daily on Day 2 and 500 mg once daily on Day 3. Walking tests will be performed on Days 1 and 3 of the treatment period.
PlaceboDrug
Placebo capsules twice daily on Day 1, a first dose at t = 0 hrs, and a second dose at t = 12 hrs. Three times daily on Day 2, and 2 capsules on the morning of Day 3. Walking tests will be performed on Days 1 and 3 of the treatment period.
UltracetDrug
Ultracet (tramadol/acetaminophen) 37.5/325 mg/mg capsules twice daily on Day 1, a first dose at t = 0 hrs, and a second dose at t = 12 hrs. Three times daily on Day 2, and two 37.5/325 mg capsules on the morning of Day 3. Walking tests will be performed on Days 1 and 3 of the treatment period.

Study groups in NCT00772967
Study group	Role	What they receive
Placebo, Naproxen, Ultracet	Experimental	Participants were treated with Placebo for 3 days in Treatment Period 1, Naproxen for 3 days in Treatment Period 2, and Ultracet for 3 days in Treatment Period 3. The treatment periods were separated by a 4-6 day break. Receives: Drug: Naproxen; Drug: Placebo; Drug: Ultracet
Naproxen, Ultracet, Placebo	Experimental	Participants were treated with Naproxen for 3 days in Treatment Period 1, Ultracet for 3 days in Treatment Period 2, and Placebo for 3 days in Treatment Period 3. The treatment periods were separated by a 4-6 day break. Receives: Drug: Naproxen; Drug: Placebo; Drug: Ultracet
Ultracet, Placebo, Naproxen	Experimental	Participants were treated with Ultracet for 3 days in Treatment Period 1, Placebo for 3 days in Treatment Period 2, and Naproxen for 3 days in Treatment Period 3. The treatment periods were separated by a 4-6 day break. Receives: Drug: Naproxen; Drug: Placebo; Drug: Ultracet
Placebo, Ultracet, Naproxen	Experimental	Participants were treated with Placebo for 3 days in Treatment Period 1, Ultracet for 3 days in Treatment Period 2, and Naproxen for 3 days in Treatment Period 3. The treatment periods were separated by a 4-6 day break. Receives: Drug: Naproxen; Drug: Placebo; Drug: Ultracet
Naproxen, Placebo, Ultracet	Experimental	Participants were treated with Naproxen for 3 days in Treatment Period 1, Placebo for 3 days in Treatment Period 2, and Ultracet for 3 days in Treatment Period 3. The treatment periods were separated by a 4-6 day break. Receives: Drug: Naproxen; Drug: Placebo; Drug: Ultracet
Ultracet, Naproxen, Placebo	Experimental	Participants were treated with Ultracet for 3 days in Treatment Period 1, Naproxen for 3 days in Treatment Period 2, and Placebo for 3 days in Treatment Period 3. The treatment periods were separated by a 4-6 day break. Receives: Drug: Naproxen; Drug: Placebo; Drug: Ultracet

What is being measured

The primary outcome is the main question the study is designed to answer.

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
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.
Measured: Baseline and Day 3

Secondary outcomes (3)

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
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.
Measured: Baseline and Day 1
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
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.
Measured: Baseline and Day 1
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
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.
Measured: Baseline and Day 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2008Nov 2008

First posted15 Oct 2008 (estimated)
Study startJun 2008
Primary completionNov 2008
Study completionNov 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for OsteoarthritisStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 22 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00772967
Sponsor's protocol ID: 0000-105
Other IDs: 2008_566
Status last verified: Oct 2015
First submitted: 13 Oct 2008
Last updated: 20 Nov 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Peeva E, Beals CR, Bolognese JA, Kivitz AJ, Taber L, Harman A, Smugar SS, Moskowitz RW. A walking model to assess the onset of analgesia in osteoarthritis knee pain. Osteoarthritis Cartilage. 2010 May;18(5):646-53. doi: 10.1016/j.joca.2009.12.008. Epub 2010 Feb 6.
PubMed 20175977

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Osteoarthritis trials

Study at a glance

From the registry record, last updated by the sponsor on 20 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Double-Blind, Placebo-Controlled, 3-Period Crossover Study to Evaluate the Analgesic Effects of Naproxen and Ultracet in a Walking Model of Osteoarthritis Knee Pain
ClinicalTrials.gov ID: NCT00772967
Acronym / sponsor ID: 0000-105
Conditions: Osteoarthritis
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 22 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: Jun 2008
Primary completion: Nov 2008 (actual)
Study completion: Nov 2008 (actual)
First posted: 15 Oct 2008 (estimated)
Results: Posted 5 Dec 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 6

Arm	Type	Receives
Placebo, Naproxen, Ultracet	Experimental	Drug: Naproxen, Drug: Placebo, Drug: UltracetParticipants were treated with Placebo for 3 days in Treatment Period 1, Naproxen for 3 days in Treatment Period 2, and Ultracet for 3 days in Treatment Period 3. The treatment periods were separated by a 4-6 day break.
Naproxen, Ultracet, Placebo	Experimental	Drug: Naproxen, Drug: Placebo, Drug: UltracetParticipants were treated with Naproxen for 3 days in Treatment Period 1, Ultracet for 3 days in Treatment Period 2, and Placebo for 3 days in Treatment Period 3. The treatment periods were separated by a 4-6 day break.
Ultracet, Placebo, Naproxen	Experimental	Drug: Naproxen, Drug: Placebo, Drug: UltracetParticipants were treated with Ultracet for 3 days in Treatment Period 1, Placebo for 3 days in Treatment Period 2, and Naproxen for 3 days in Treatment Period 3. The treatment periods were separated by a 4-6 day break.
Placebo, Ultracet, Naproxen	Experimental	Drug: Naproxen, Drug: Placebo, Drug: UltracetParticipants were treated with Placebo for 3 days in Treatment Period 1, Ultracet for 3 days in Treatment Period 2, and Naproxen for 3 days in Treatment Period 3. The treatment periods were separated by a 4-6 day break.
Naproxen, Placebo, Ultracet	Experimental	Drug: Naproxen, Drug: Placebo, Drug: UltracetParticipants were treated with Naproxen for 3 days in Treatment Period 1, Placebo for 3 days in Treatment Period 2, and Ultracet for 3 days in Treatment Period 3. The treatment periods were separated by a 4-6 day break.
Ultracet, Naproxen, Placebo	Experimental	Drug: Naproxen, Drug: Placebo, Drug: UltracetParticipants were treated with Ultracet for 3 days in Treatment Period 1, Naproxen for 3 days in Treatment Period 2, and Placebo for 3 days in Treatment Period 3. The treatment periods were separated by a 4-6 day break.

Who may qualify

Ages: 45 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Has osteoarthritis of the knee and primary source of pain is knee
Females must not be pregnant or nursing and must agree to use birth control throughout the study
Is willing to limit alcohol and caffeine intake
Is willing to abstain from smoking during study visits
Must be able to walk on a treadmill at a pace of at least 1 mile/hour

Key exclusion criteria (7 listed)

Has a medical/arthritic disease that would interfere with evaluation
Is unable to take naproxen or Ultracet
Has congestive heart failure or angina
Has a history of stroke
Has a history of uncontrolled high blood pressure

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NaproxenNaproxen tablets 500 mg twice daily on Day 1, a first dose at t = 0 hrs, and a second dose at t = 12 hrs. Twice daily on Day 2 and 500 mg once daily on Day 3. Walking tests will be performed on Days 1 and 3 of the treatment period.	Drug	Naproxen, Placebo, Ultracet, Naproxen, Ultracet, Placebo, Placebo, Naproxen, Ultracet, Placebo, Ultracet, Naproxen, Ultracet, Naproxen, Placebo, Ultracet, Placebo, Naproxen
PlaceboPlacebo capsules twice daily on Day 1, a first dose at t = 0 hrs, and a second dose at t = 12 hrs. Three times daily on Day 2, and 2 capsules on the morning of Day 3. Walking tests will be performed on Days 1 and 3 of the treatment period.	Drug	Naproxen, Placebo, Ultracet, Naproxen, Ultracet, Placebo, Placebo, Naproxen, Ultracet, Placebo, Ultracet, Naproxen, Ultracet, Naproxen, Placebo, Ultracet, Placebo, Naproxen
UltracetUltracet (tramadol/acetaminophen) 37.5/325 mg/mg capsules twice daily on Day 1, a first dose at t = 0 hrs, and a second dose at t = 12 hrs. Three times daily on Day 2, and two 37.5/325 mg capsules on the morning of Day 3. Walking tests will be performed on Days 1 and 3 of the treatment period.	Drug	Naproxen, Placebo, Ultracet, Naproxen, Ultracet, Placebo, Placebo, Naproxen, Ultracet, Placebo, Ultracet, Naproxen, Ultracet, Naproxen, Placebo, Ultracet, Placebo, Naproxen

Primary outcome

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
Time frame: Baseline and Day 3
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.

3 secondary outcomes

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
Time frame: Baseline and Day 1
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
Time frame: Baseline and Day 1
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
Time frame: Baseline and Day 3

Results and safety

Results posted to the registry on 5 Dec 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo, Naproxen, Ultracet	3	3
Naproxen, Ultracet, Placebo	5	5
Ultracet, Placebo, Naproxen	3	3
Placebo, Ultracet, Naproxen	4	3
Naproxen, Placebo, Ultracet	4	4
Ultracet, Naproxen, Placebo	3	3

Primary outcome: 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

Time frame: Baseline and Day 3. Least squares mean (95% Confidence Interval). Unit: units on a scale

Measure	Placebo n = 20	Naproxen n = 21	Ultracet n = 19
Value	-0.927 (-1.52 to -0.33)	-1.54 (-2.12 to -0.96)	-1.73 (-2.34 to -1.12)

Placebo vs Naproxen: Mean Difference (Final Values): -0.611 (90% CI -1.36 to 0.14), p = 0.089, ANCOVA
Placebo vs Ultracet: Mean Difference (Final Values): -0.804 (90% CI -1.57 to -0.04), p = 0.043, ANCOVA

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

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 22 (0%)	0 of 22 (0%)	Not reported
Naproxen	0 of 22 (0%)	0 of 22 (0%)	Not reported
Ultracet	0 of 20 (0%)	2 of 20 (10%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 20175977Peeva E, Beals CR, Bolognese JA, Kivitz AJ, Taber L, Harman A, Smugar SS, Moskowitz RW. A walking model to assess the onset of analgesia in osteoarthritis knee pain. Osteoarthritis Cartilage. 2010 May;18(5):646-53. doi: 10.1016/j.joca.2009.12.008. Epub 2010 Feb 6.

Related trials for Osteoarthritis

Not yet recruiting
Holistic Healing for Knee Osteoarthritis
Knee Osteoarthritis (Knee OA)
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Effectiveness of Therapeutic Exercises on Spinopelvic Mobility
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Recruiting
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Monitor study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Naproxen and Ultracet in people with Osteoarthritis, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Baseline and Day 3). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00772967, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2015.