Efficacy and Safety Study Evaluating ADL5859 and ADL5747 in Participants With Pain Due to Osteoarthritis of the Knee

ID: NCT00979953
Status: Completed
Phase: Phase 2
Start Date: October 01, 2009
First Submitted: September 17, 2009
Last Updated: July 27, 2015
Results: Available
Success Rate: 89%
Sponsors & Collaborators: Cubist Pharmaceuticals LLC, Pfizer
Location: United States
Conditions: Osteoarthritis of the Knee
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Study Description

Brief Summary

The purpose of this study is to determine the efficacy of ADL5859 versus placebo and ADL5747 versus placebo in relieving pain in participants with osteoarthritis of the knee.

Detailed Description

Condition or disease Intervention/treatment Phase

Osteoarthritis of the Knee

Drug: ADL5859
Other Names
Drug: ADL5747
Other Names
Drug: Oxycodone CR
Other Names
OxyContin
Drug: Placebo
Other Names
Phase 2

Tracking Information

First Submitted DateSeptember 17, 2009
Last Update Posted DateJuly 27, 2015
Start DateOctober 01, 2009
Actual Completion DateJune 01, 2010
Primary Completion DateApril 01, 2010
Results First Submitted DateApril 21, 2015
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Change From Baseline in the Average Pain Score (NPRS) for Week 2 [Time Frame: Baseline, Week 2]

    The mean of the daily average scores were calculated from the NPRS pain assessment for the previous 24 hours obtained once a day for at least 4 days from Day -6 through Day 1 (Baseline assessment) and everyday from Day 2 through Day 15 (Treatment Phase assessment). The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain.

Original Primary Outcome Measures

  • Change From Baseline in the Average Pain Score (NPRS) for Week 2

    The mean of the daily average scores were calculated from the NPRS pain assessment for the previous 24 hours obtained once a day for at least 4 days from Day -6 through Day 1 (Baseline assessment) and everyday from Day 2 through Day 15 (Treatment Phase assessment). The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain.

Current Secondary Outcome Measures

Not Available

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleEfficacy and Safety Study Evaluating ADL5859 and ADL5747 in Participants With Pain Due to Osteoarthritis of the Knee
Official TitleA Phase 2a, Randomized, Double-blind, Placebo- and Active-controlled, Parallel-group, Multicenter Study Evaluating the Analgesic Efficacy and Safety of ADL5859 and ADL5747 in Subjects With Moderate to Severe Pain Due to Osteoarthritis of the Knee
Brief Summary

The purpose of this study is to determine the efficacy of ADL5859 versus placebo and ADL5747 versus placebo in relieving pain in participants with osteoarthritis of the knee.

Detailed Description

Study TypeInterventional
Study PhasePhase 2
Estimated Enrollment
408
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
Quadruple
Primary Purpose
Treatment
Conditions
Osteoarthritis of the Knee
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: ADL5859

Other Names
Drug: ADL5747

Other Names
Drug: Oxycodone CR

Other Names
OxyContin
Drug: Placebo

Other Names
Study Groups/Cohorts
ADL5859
One 50-milligrams (mg) ADL5859 capsule, one 100-mg ADL5859 capsule, and 2 placebo capsules administered orally twice daily (BID) for 14 days

ADL5747
One 150-mg ADL5747 capsule and 3 placebo capsules administered orally BID for 14 days

Oxycodone CR
One 10-mg Oxycodone controlled release (CR) capsule and 3 placebo capsules administered orally BID Days 1 through 4 One 20-mg Oxycodone CR capsule and 3 placebo capsules administered orally BID Days 5 through 14

Placebo
Four placebo capsules administered orally BID for 14 days

Study Arms
Experimental ADL5747
One 150-mg ADL5747 capsule and 3 placebo capsules administered orally BID for 14 days
Drug : ADL5747

Experimental ADL5747
One 150-mg ADL5747 capsule and 3 placebo capsules administered orally BID for 14 days
Drug : Placebo

Experimental ADL5859
One 50-milligrams (mg) ADL5859 capsule, one 100-mg ADL5859 capsule, and 2 placebo capsules administered orally twice daily (BID) for 14 days
Drug : ADL5859

Experimental ADL5859
One 50-milligrams (mg) ADL5859 capsule, one 100-mg ADL5859 capsule, and 2 placebo capsules administered orally twice daily (BID) for 14 days
Drug : Placebo

Active Comparator Oxycodone CR
One 10-mg Oxycodone controlled release (CR) capsule and 3 placebo capsules administered orally BID Days 1 through 4 One 20-mg Oxycodone CR capsule and 3 placebo capsules administered orally BID Days 5 through 14
Drug : Oxycodone CR

Active Comparator Oxycodone CR
One 10-mg Oxycodone controlled release (CR) capsule and 3 placebo capsules administered orally BID Days 1 through 4 One 20-mg Oxycodone CR capsule and 3 placebo capsules administered orally BID Days 5 through 14
Drug : Placebo

Placebo Comparator Placebo
Four placebo capsules administered orally BID for 14 days
Drug : Placebo

Arm Intervention/Treatment
Experimental ADL5747
One 150-mg ADL5747 capsule and 3 placebo capsules administered orally BID for 14 days
Drug : ADL5747
Experimental ADL5747
One 150-mg ADL5747 capsule and 3 placebo capsules administered orally BID for 14 days
Drug : Placebo
Experimental ADL5859
One 50-milligrams (mg) ADL5859 capsule, one 100-mg ADL5859 capsule, and 2 placebo capsules administered orally twice daily (BID) for 14 days
Drug : ADL5859
Experimental ADL5859
One 50-milligrams (mg) ADL5859 capsule, one 100-mg ADL5859 capsule, and 2 placebo capsules administered orally twice daily (BID) for 14 days
Drug : Placebo
Active Comparator Oxycodone CR
One 10-mg Oxycodone controlled release (CR) capsule and 3 placebo capsules administered orally BID Days 1 through 4 One 20-mg Oxycodone CR capsule and 3 placebo capsules administered orally BID Days 5 through 14
Drug : Oxycodone CR
Active Comparator Oxycodone CR
One 10-mg Oxycodone controlled release (CR) capsule and 3 placebo capsules administered orally BID Days 1 through 4 One 20-mg Oxycodone CR capsule and 3 placebo capsules administered orally BID Days 5 through 14
Drug : Placebo
Placebo Comparator Placebo
Four placebo capsules administered orally BID for 14 days
Drug : Placebo

Recruitment Information

Recruitment Status:Completed
Enrollment408
Completion DateJune 01, 2010
Eligibility Criteria: Key Inclusion Criteria:
- a man or woman between 18 and 75 years of age, inclusive
- for women of childbearing potential, be using an insertable, injectable, transdermal, or combination oral contraceptive deemed highly effective by the United States Food and Drug Administration from the first dose of study medication through the end of the study and have negative findings on pregnancy tests performed at screening and randomization (women who are surgically sterile [for example, hysterectomy, tubal ligation] or postmenopausal [if ≥55 years old, no menses for at least 2 years; if <55 years old, follicle-stimulating hormone concentrations within the postmenopausal range of >40 milli-international units per milliliter (mIU/mL) and 17 β-estradiol levels of <37 picograms per milliliter (pg/mL)] are also eligible to participate)
- for male participants, be surgically sterile or agree to use an appropriate method of contraception (that is, use a barrier method in conjunction with spermicide or have a sexual partner who is surgically sterile, postmenopausal, or using an insertable, injectable, transdermal, or combination oral contraceptive deemed highly effective by the United States Food and Drug Administration) from the first dose of study medication through the end of the study
- have a body weight between 45 and 150 kilograms (kg), inclusive
- have had pain in the index knee for at least the past 6 months
- meet the following criteria for osteoarthritis of the knee established by the American College of Rheumatology (radiographs must have been taken within the last year; if none is available, a radiograph must be taken and the diagnostic criteria must be confirmed before the participant is enrolled in the study): have index knee pain plus at least 1 moderate or definite osteophyte on radiographs. Must also have at least 1 of the following: be more than 50 years old, have morning stiffness for less than 30 minutes, or have crepitus on active motion
- have an average weekly pain score of at least 4.00 on the numeric pain rating scale (NPRS) for the index knee during the baseline week before randomization (to be eligible for randomization, participants must report their NPRS score via the interactive voice-response system (IVRS) for at least 4 of the 7 days immediately before randomization, with the first score being recorded on Day -6)
- if receiving nonselective or selective cyclooxygenase (COX) inhibitors, have a stable daily dose regimen for at least 4 weeks before screening; if receiving nonselective or selective COX inhibitors on an as needed basis, have discontinued use by Day -14; if receiving angiotensin-converting enzyme (ACE) inhibitors, have a stable dose regimen for at least 4 weeks before screening
Key
Exclusion Criteria:
- have undergone arthroscopy on the index knee within 6 months before study entry
- have other severe pain that, in the opinion of the investigator, may impair the assessment of the pain due to osteoarthritis
- have a history of hypersensitivity or intolerance to opioids (including tramadol and tapentadol)
- have, as determined by the investigator or the sponsor's medical monitor, a history or clinical manifestations of significant renal, hepatic, hematologic, cardiovascular, metabolic, gastrointestinal, neurologic, psychiatric, or another condition that would preclude participation in the study or affect the outcome of the study
- have taken oral or intramuscular corticosteroids within 30 days before study entry (inhaled or topical corticosteroids are permitted)
- have received intra-articular injections of corticosteroids into the index joint within 12 weeks before screening
- have received intra-articular injections of hyaluronic acid into the index joint within 24 weeks before screening
- currently taking medications other than nonsteroidal anti-inflammatory drugs prescribed for chronic pain (such as duloxetine or pregabalin)
GenderAll
Age18 Years to 75 Years
Accepts Healthy VolunteersNo
Contacts
Not Available
Listed Location Countries
United States

Administrative Information

NCT Number:NCT00979953
Other Study ID Numbers
44CL240
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Cubist Pharmaceuticals LLC
Collaborators
Pfizer
Investigators
Study Director
Bruce Berger, MD
Cubist Pharmaceuticals LLC

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Not Available

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Not Available

Reporting Groups

TitleDescription
ADL5859
One 50-milligrams (mg) ADL5859 capsule, one 100-mg ADL5859 capsule, and 2 placebo capsules administered orally twice daily (BID) for 14 days
ADL5747
One 150-mg ADL5747 capsule and 3 placebo capsules administered orally BID for 14 days
Oxycodone CR
One 10-mg Oxycodone controlled release (CR) capsule and 3 placebo capsules administered orally BID Days 1 through 4 One 20-mg Oxycodone CR capsule and 3 placebo capsules administered orally BID Days 5 through 14
Placebo
Four placebo capsules administered orally BID for 14 days

Participant Flow: Overall

ADL5859ADL5747Oxycodone CRPlacebo
10199104104
Started10199104104
Completed93948297
Not Completed85227
Adverse Event52174
Lack of Efficacy1200
Lost to Follow-up1110
Protocol Violation1022
Withdrawal by Subject0021

Baseline Characteristics

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants received at least 1 dose of study drug.

Reporting Groups

TitleDescription
ADL5859
One 50-mg ADL5859 capsule, one 100-mg ADL5859 capsule, and 2 placebo capsules administered orally BID for 14 days
ADL5747
One 150-mg ADL5747 capsule and 3 placebo capsules administered orally BID for 14 days
Oxycodone CR
One 10-mg Oxycodone CR capsule and 3 placebo capsules administered orally BID Days 1 through 4 One 20-mg Oxycodone CR capsule and 3 placebo capsules administered orally BID Days 5 through 14
Placebo
Four placebo capsules administered orally BID for 14 days
Total
Total of all reporting groups

Baseline Measures

ADL5859ADL5747Oxycodone CRPlaceboTotal
Overall Participants Analyzed
Units: Participants
Participants Analyzed
10199104104408
10199104104408
Age
Units: years - Mean (Standard Deviation)
Participants Analyzed
10199104104408
56.5 (8.15)57.3 (8.74)57.8 (8.39)56.5 (8.11)57.0 (8.34)
Gender
Units: participants - Number
Participants Analyzed
10199104104408
Female59576361240
Male42424143168

Outcome Measures

1. Primary: Change From Baseline in the Average Pain Score (NPRS) for Week 2

Measure Type
Primary
Measure Title
Change From Baseline in the Average Pain Score (NPRS) for Week 2
Measure Description
The mean of the daily average scores were calculated from the NPRS pain assessment for the previous 24 hours obtained once a day for at least 4 days from Day -6 through Day 1 (Baseline assessment) and everyday from Day 2 through Day 15 (Treatment Phase assessment). The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain.
Time Frame
Baseline, Week 2

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least 1 dose of study medication and had at least evaluable 1 NPRS postdose measurement. Last-observation-carried-forward (LOCF) was used to impute missing postbaseline values.

Reporting Groups

TitleDescription
Placebo
Four placebo capsules administered orally BID for 14 days
Oxycodone CR
One 10-mg Oxycodone CR capsule and 3 placebo capsules administered orally BID Days 1 through 4 One 20-mg Oxycodone CR capsule and 3 placebo capsules administered orally BID for Days 5 through 14
ADL5747
One 150-mg ADL5747 capsule and 3 placebo capsules administered orally BID for 14 days
ADL5859
One 50-mg ADL5859 capsule, one 100-mg ADL5859 capsule, and 2 placebo capsules administered orally BID for 14 days

Outcome Measures

PlaceboOxycodone CRADL5747ADL5859
Participants Analyzed
Units: Participants
10310099101
Change From Baseline in the Average Pain Score (NPRS) for Week 2
Units: units on a scale - Least Squares Mean (Standard Deviation)
-2.20 (2.088)-2.24 (2.162)-1.57 (1.656)-1.77 (1.776)

Serious Adverse Events

Time Frame
Not Available
Additional Description
Not Available
Frequency Threshold0% (Threshold above which other adverse events are reported)

Reporting Groups

TitleDescription
ADL5859
One 50-mg ADL5859 capsule, one 100-mg ADL5859 capsule, and 2 placebo capsules administered orally BID for 14 days
ADL5747
One 150-mg ADL5747 capsule and 3 placebo capsules administered orally BID for 14 days
Oxycodone CR
One 10-mg Oxycodone CR capsule and 3 placebo capsules administered orally BID Days 1 through 4 One 20-mg Oxycodone CR capsule and 3 placebo capsules administered orally BID Days 5 through 14
Placebo
Four placebo capsules administered orally BID for 14 days

Serious Adverse Events

ADL5859ADL5747Oxycodone CRPlacebo
Total, serious adverse events
No. of participants affected / at risk2/101 (0.00%)1/99 (0.00%)0/104 (0.00%)1/104 (0.00%)
Atrial fibrillation
No. of participants affected / at risk0/101 (0.00%)0/99 (0.00%)0/104 (0.00%)1/104 (0.00%)
Biliary dyskinesia
No. of participants affected / at risk1/101 (0.00%)0/99 (0.00%)0/104 (0.00%)0/104 (0.00%)
Cerebral Haemorrhage
No. of participants affected / at risk0/101 (0.00%)1/99 (0.00%)0/104 (0.00%)0/104 (0.00%)
Chronic Obstructive Pulmonary Disease (COPD)
No. of participants affected / at risk1/101 (0.00%)0/99 (0.00%)0/104 (0.00%)0/104 (0.00%)

Other Adverse Events

Time Frame
Not Available
Additional Description
Not Available
Frequency Threshold5% (Threshold above which other adverse events are reported)

Reporting Groups

TitleDescription
ADL5859
One 50-mg ADL5859 capsule, one 100-mg ADL5859 capsule, and 2 placebo capsules administered orally BID for 14 days
ADL5747
One 150-mg ADL5747 capsule and 3 placebo capsules administered orally BID for 14 days
Oxycodone CR
One 10-mg Oxycodone CR capsule and 3 placebo capsules administered orally BID Days 1 through 4 One 20-mg Oxycodone CR capsule and 3 placebo capsules administered orally BID Days 5 through 14
Placebo
Four placebo capsules administered orally BID for 14 days

Other Adverse Events

ADL5859ADL5747Oxycodone CRPlacebo
Total, other adverse events
No. of participants affected / at risk50/101 (0.00%)40/99 (0.00%)75/104 (0.00%)37/104 (0.00%)
Constipation
No. of participants affected / at risk8/101 (0.00%)5/99 (0.00%)30/104 (0.00%)4/104 (0.00%)
Diarrhea
No. of participants affected / at risk5/101 (0.00%)7/99 (0.00%)3/104 (0.00%)1/104 (0.00%)
Dry mouth
No. of participants affected / at risk8/101 (0.00%)6/99 (0.00%)13/104 (0.00%)6/104 (0.00%)
Nausea
No. of participants affected / at risk5/101 (0.00%)5/99 (0.00%)32/104 (0.00%)4/104 (0.00%)
Vomiting
No. of participants affected / at risk1/101 (0.00%)0/99 (0.00%)15/104 (0.00%)0/104 (0.00%)
Fatigue
No. of participants affected / at risk6/101 (0.00%)2/99 (0.00%)17/104 (0.00%)7/104 (0.00%)
Dizziness
No. of participants affected / at risk4/101 (0.00%)1/99 (0.00%)17/104 (0.00%)2/104 (0.00%)
Headache
No. of participants affected / at risk10/101 (0.00%)10/99 (0.00%)13/104 (0.00%)3/104 (0.00%)
Somnolence
No. of participants affected / at risk7/101 (0.00%)4/99 (0.00%)20/104 (0.00%)8/104 (0.00%)
Disturbance in attention
No. of participants affected / at risk2/101 (0.00%)0/99 (0.00%)8/104 (0.00%)0/104 (0.00%)
Pruritus
No. of participants affected / at risk1/101 (0.00%)0/99 (0.00%)17/104 (0.00%)2/104 (0.00%)

More Information

Certain Agreements

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

Results Point of Contact

Name/TitleOrganizationPhoneEmail
VP of Clinical Research
Cubist Pharmaceuticals
(781) 860-8660