Back to resultsPhase 2 Efficacy Trial of OLT1177 Gel in Subjects With Moderate to Severe Pain Associated With OA of the Knee
Primary Purpose
Osteoarthritis of the Knee
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
OLT1177 Gel
Placebo gel
Sponsored by
About this trial
This is an interventional treatment trial for Osteoarthritis of the Knee focused on measuring Knee, Osteoarthritis, OA, Knee pain, Moderate pain, Severe pain, Inflammation, Safety, Efficacy, Randomized, Topical, Gel, Olatec, OLT1177, Joint Diseases, Musculoskeletal Diseases, Rheumatic Diseases, Arthritis, Therapeutic, Analgesic
Eligibility Criteria
Inclusion Criteria:
- Age 35 to 80
- Subjects of childbearing potential and their partners must use effective contraception
- OA based on the ACR criteria
- OA of the knee ≥ 6 months prior to Screening
- OA knee pain which required NSAID or other therapy for ≥ 15 days
- Pain on Movement in the contralateral knee be ≤ 20 mm
- Radiographic evidence of OA by Kellgren-Lawrence score of 2 or 3 taken 6 months prior to Screening
- Moderate to severe OA pain defined as POM score between 50 mm and 90 mm
- Baseline WOMAC pain subscale score ≥ 9
- No change in physical activity and/or therapy for the past 3 months
- Provide written informed consent and comply with the trial
Exclusion Criteria:
- Use of Rescue Medication or any other pain medication 48 hours prior to Baseline visit
- Inflammatory skin condition over the target knee
- Extreme pain in the target knee characterized by POM score of > 90 mm
- Mild pain in the target knee, characterized by POM score of < 50 mm
- > 30 mm POM score variability in Days -2 to -1 from Baseline visit
- Baseline POM score of > 20 mm for the contralateral knee or any other significant joint or general pain at Baseline visit
- Excessive effusion in the target knee
- Heat and/or redness in comparison to the contralateral knee
- Knock-kneed or bow-legged defined by valgus or varus deformity of ≥ 15 degrees
- Acute or chronic injury other than OA
- Radiographic evidence of OA by Kellgren-Lawrence score of 0, 1 or 4
- Open surgery of the target knee within the last year
- Arthroscopic surgery of the target knee within the last 6 months
- Surgery of the target knee requiring insertion of a medical device or surgical hardware
Use of prohibited concomitant medications/therapies during the 7-day washout period or planned use during the 14-day treatment period including:
- Prescription medications to treat pain, OTC and natural supplements
- Muscle relaxants unless on a stable dose ≥ 30 days prior to Screening
- Nutraceuticals unless on a stable dose ≥ 3 months prior to Screening
- Sedative hypnotics unless on a stable dose ≥ 30 days prior to Screening
- Devices or therapeutic treatments for knee pain or ambulation
- Systemic corticosteroids
- Other Investigational Drugs
- Chemotherapeutic drugs
- Immunotherapy
- Topical products applied to the target knee
- Cyclosporine (except ophthalmic), lithium, methotrexate
- Anti-depressants or medications acting on the central nervous system, unless on a stable dose for depression ≥ 3 months prior to Screening
- Narcotics or previous history of chronic narcotic use
- Rescue Medication within 48 hours of Baseline, Day 7 or Day 14 visits
- Intraarticular steroids in the target knee within the previous 3 months or in any other joint within the previous 30 days
- Intraarticular hyaluronate within the previous 6 months or in any other joint within the previous 30 days
- Systemic corticosteroids within the prior month
- Documented history of inflammatory joint disease
- BMI over 35
- Uncontrolled psychiatric conditions
- Cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematological or neurological disease or prior surgery
- Uncontrolled hypertension
- Diabetes with an HbA1c level > 8
- Known positive for HIV, Hepatitis B surface antigen (HBsAg) or antibodies to Hepatitis C Virus (HCV)
- Cancer within the past 5 years, except for treated basal cell or squamous cell carcinoma of the skin
- Any other medical conditions, diseases or prior surgeries
- Interventional and/or surgical procedure during the 28 days following randomization
- Change in level of physical activity during the 28 days following randomization
- Active infection or fever ≥ 38°C within 3 days of Baseline visit
- Known sensitivity to Investigational Drug
- Women planning to become pregnant during the 28-day trial
- Participation in any Investigational Drug or device trial within 30-day prior to Baseline visit
Sites / Locations
- Avail Clinical Research
- Miami Research Associates
- Wake Research Associates
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
OLT1177 Gel
Placebo gel
Arm Description
4 mL per dose, applied 3 times per day on Days 1 - 13 with only one dose administered on Day 14, assuming TID on Day 1
Identical dose and dosing regimen as the Investigational Drug (OLT1177 Gel)
Outcomes
Primary Outcome Measures
Change in WOMAC knee pain subscale (scale 0 - 20)
The mean group change for OLT1177 Gel and vehicle control from Baseline (Day 0) to Day 14 in WOMAC knee pain subscale (Scale 0-20), which is determined by the subjects responses to five questions (S1-S5) using a 5-point Likert scale (i.e., 'none'=0; 'mild'=1, 'moderate'=2; 'severe'=3; 'extreme'=4)
Secondary Outcome Measures
Change in Current Knee Pain (100-mm VAS)
The mean group change in Current Knee Pain (100-mm VAS) for OLT1177 Gel and vehicle control from Baseline (Day 0) pre-dose to Day 1, 50-minutes post-dose (± 10 minutes) calculated in millimeters and percentage, as recorded by the subjects during the Baseline (Day 0) visit after the first application of the Investigational Drug
Mean group rating of Relative Knee Pain (5-point scale)
The mean group rating of Relative Knee Pain (5-point scale) for OLT1177 Gel and vehicle control at Day 1, 50-minutes post-dose (± 10 minutes) as recorded by the subjects during the Baseline (Day 0) visit after the first application of the Investigational Drug
Change in WOMAC knee pain subscale
The mean group change for OLT1177 Gel and vehicle control from Baseline (Day 0) to Day 7 in WOMAC knee pain subscale (Scale 0-20), which is determined by the subjects responses to five questions during the Day 7 site visit
Change in Pain on Movement (100-mm VAS)
The mean group change in Pain on Movement (100-mm VAS) for OLT1177 Gel and vehicle control from Baseline (Day 0) to Day 7, calculated in millimeters and percentage, as recorded by the subjects while at home
Change in Pain on Movement (100-mm VAS)
The mean group change in Pain on Movement (100-mm VAS) for OLT1177 Gel and vehicle control from Baseline (Day 0) to Day 14, calculated in millimeters and percentage, as recorded by the subjects while at home
Change in Global Rating of Disease
The mean group change in Global Rating of Disease for OLT1177 Gel and vehicle control from Baseline (Day 0) to Day 14 measured on a 5-point Likert scale, with numerical values to be assigned as follows: 0 = poor, 1 = fair, 2 = good, 3 = very good and 4 = excellent, as recorded by the subjects at the Day 14 site visit
Change in Global Evaluation of Treatment
The mean group rating of Global Evaluation of Treatment for OLT1177 Gel and vehicle control at Day 14 measured on a 5-point Likert scale, with numerical values to be assigned as follows: 0 = poor, 1 = fair, 2 = good, 3 = very good and 4 = excellent, as recorded by the subjects at the Day 14 site visit
Change in WOMAC Stiffness subscale (Scale 0-8)
The mean group change for OLT1177 Gel and vehicle control from Baseline (Day 0) to Day 7 in the WOMAC Stiffness subscale (Scale 0-8) and in the WOMAC Physical function subscale (Scale 0-68), which is determined by subjects responses to questions at the Day 7 site visit
Change in WOMAC Stiffness subscale (Scale 0-8)
The mean group change for OLT1177 Gel and vehicle control from Baseline (Day 0) to Day 14 in the WOMAC Stiffness subscale (Scale 0-8) and in the WOMAC Physical function subscale (Scale 0-68), which is determined by subjects responses to questions at the Day 14 site visit
Change in the use of Rescue Medication
The mean group change for OLT1177 Gel and vehicle control in the proportion of subjects who required the use of Rescue Medication
Change in the time to use of Rescue Medication
The mean group time to use of Rescue Medication for OLT1177 Gel and vehicle control after the first dose of Investigational Drug
Proportion of subjects experiencing an improvement in WOMAC knee pain subscale
The proportion of subjects who experience an improvement in WOMAC knee pain subscale (Scale 0-20, transformed to a 0 to 100 scale) from Baseline (Day 0) to Day 14 equal to or greater than the minimum clinically important improvement (MCII) threshold of 15-mm
Proportion of subjects experiencing an improvement in WOMAC knee pain subscale
The proportion of subjects who experience an improvement in WOMAC knee pain subscale (Scale 0-20, transformed to a 0 to 100 scale) from Baseline (Day 0) to Day 14 equal to or greater than the minimum clinically important improvement (MCII) threshold of 20%
Proportion of subjects whose WOMAC knee pain subscale is less than the PASS
The proportion of subjects whose WOMAC knee pain subscale (Scale 0-20, transformed to a 0 to 100 scale) at Day 14 is less than the patient acceptable symptom state (PASS) of 40
Proportion of subjects experiencing an improvement in Pain on Movement
The proportion of subjects who experience an improvement in Pain on Movement (100-mm VAS) from Baseline (Day 0) to Day 14 equal to or greater than the minimum clinically important improvement (MCII) threshold of 15-mm
Proportion of subjects experiencing an improvement in Pain on Movement
The proportion of subjects who experience an improvement in Pain on Movement (100-mm VAS) from Baseline (Day 0) to Day 14 equal to or greater than the minimum clinically important improvement (MCII) threshold of 20%
Proportion of subjects whose POM is less than the PASS
The proportion of subjects whose Pain on Movement (100-mm VAS) at Day 14 is less than the patient acceptable symptom state (PASS) of 40-mm
Full Information
NCT ID
NCT01768975
First Posted
January 14, 2013
Last Updated
September 25, 2014
Sponsor
Olatec Therapeutics LLC
1. Study Identification
Unique Protocol Identification Number
NCT01768975
Brief Title
Phase 2 Efficacy Trial of OLT1177 Gel in Subjects With Moderate to Severe Pain Associated With OA of the Knee
Official Title
Randomized, Double-Blind, Vehicle-Controlled, Efficacy and Safety Clinical Trial of Topically Applied OLT1177 Gel in Subjects With Moderate to Severe Pain Associated With Osteoarthritis of the Knee Following Cessation of Pain Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
January 2013 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
August 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Olatec Therapeutics LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this trial is to investigate the efficacy and safety of OLT1177 Gel in subjects with moderate to severe pain associated with osteoarthritis of the knee following cessation of pain therapy.
Detailed Description
This is a randomized, double-blind, vehicle-controlled, repeat-dose, multi-center Phase 2 efficacy and safety clinical trial of subjects with moderate to severe pain associated with osteoarthritis of the knee. Eighty-four subjects, randomized in a 2:1 ratio (OLT1177 Gel to vehicle control) will receive up to 40 doses of the Investigational Drug (56 subjects OLT1177 Gel and 28 subjects vehicle control) over 14 consecutive days given 3 times per day (4 mL per dose, TID on Days 1 - 13 with only one dose administered on Day 14, assuming TID on Day 1) and will have safety data collected through Day 28. Subjects with moderate to severe pain associated with osteoarthritis of the knee will be evaluated twice for eligibility: 1) at the Screening visit; and 2) at the Baseline (Day 0) visit, after a 7-day washout period of all pain medications except for trial provided Rescue Medication (500 mg/dose of acetaminophen) for those that experience unacceptable pain during the washout and 14-day treatment period.
Subjects will be encouraged not to take any pain medication during the 7-day washout period; however, for the first 5 days they are allowed to take only Rescue Medication. No pain medication, including Rescue Medication, is allowed during the 2-day pain intensity assessment period or within 48 hours of the Baseline (Day 0), Day 7 and Day 14 visits.
Subjects will be asked to record and report their level of pain at different time points throughout the 14-day trial.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoarthritis of the Knee
Keywords
Knee, Osteoarthritis, OA, Knee pain, Moderate pain, Severe pain, Inflammation, Safety, Efficacy, Randomized, Topical, Gel, Olatec, OLT1177, Joint Diseases, Musculoskeletal Diseases, Rheumatic Diseases, Arthritis, Therapeutic, Analgesic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
79 (Actual)
8. Arms, Groups, and Interventions
Arm Title
OLT1177 Gel
Arm Type
Experimental
Arm Description
4 mL per dose, applied 3 times per day on Days 1 - 13 with only one dose administered on Day 14, assuming TID on Day 1
Arm Title
Placebo gel
Arm Type
Placebo Comparator
Arm Description
Identical dose and dosing regimen as the Investigational Drug (OLT1177 Gel)
Intervention Type
Drug
Intervention Name(s)
OLT1177 Gel
Other Intervention Name(s)
OLT1177
Intervention Description
4 mL per dose, applied 3 times per day on Days 1 - 13 with only one dose administered on Day 14, assuming TID on Day 1
Intervention Type
Other
Intervention Name(s)
Placebo gel
Intervention Description
Identical dose and dosing regimen as the Investigational Drug (OLT1177 Gel)
Primary Outcome Measure Information:
Title
Change in WOMAC knee pain subscale (scale 0 - 20)
Description
The mean group change for OLT1177 Gel and vehicle control from Baseline (Day 0) to Day 14 in WOMAC knee pain subscale (Scale 0-20), which is determined by the subjects responses to five questions (S1-S5) using a 5-point Likert scale (i.e., 'none'=0; 'mild'=1, 'moderate'=2; 'severe'=3; 'extreme'=4)
Time Frame
14 days
Secondary Outcome Measure Information:
Title
Change in Current Knee Pain (100-mm VAS)
Description
The mean group change in Current Knee Pain (100-mm VAS) for OLT1177 Gel and vehicle control from Baseline (Day 0) pre-dose to Day 1, 50-minutes post-dose (± 10 minutes) calculated in millimeters and percentage, as recorded by the subjects during the Baseline (Day 0) visit after the first application of the Investigational Drug
Time Frame
50 minutes post dose (± 10 minutes)
Title
Mean group rating of Relative Knee Pain (5-point scale)
Description
The mean group rating of Relative Knee Pain (5-point scale) for OLT1177 Gel and vehicle control at Day 1, 50-minutes post-dose (± 10 minutes) as recorded by the subjects during the Baseline (Day 0) visit after the first application of the Investigational Drug
Time Frame
50 minutes post dose (± 10 minutes)
Title
Change in WOMAC knee pain subscale
Description
The mean group change for OLT1177 Gel and vehicle control from Baseline (Day 0) to Day 7 in WOMAC knee pain subscale (Scale 0-20), which is determined by the subjects responses to five questions during the Day 7 site visit
Time Frame
7 days
Title
Change in Pain on Movement (100-mm VAS)
Description
The mean group change in Pain on Movement (100-mm VAS) for OLT1177 Gel and vehicle control from Baseline (Day 0) to Day 7, calculated in millimeters and percentage, as recorded by the subjects while at home
Time Frame
7 days
Title
Change in Pain on Movement (100-mm VAS)
Description
The mean group change in Pain on Movement (100-mm VAS) for OLT1177 Gel and vehicle control from Baseline (Day 0) to Day 14, calculated in millimeters and percentage, as recorded by the subjects while at home
Time Frame
14 days
Title
Change in Global Rating of Disease
Description
The mean group change in Global Rating of Disease for OLT1177 Gel and vehicle control from Baseline (Day 0) to Day 14 measured on a 5-point Likert scale, with numerical values to be assigned as follows: 0 = poor, 1 = fair, 2 = good, 3 = very good and 4 = excellent, as recorded by the subjects at the Day 14 site visit
Time Frame
14 days
Title
Change in Global Evaluation of Treatment
Description
The mean group rating of Global Evaluation of Treatment for OLT1177 Gel and vehicle control at Day 14 measured on a 5-point Likert scale, with numerical values to be assigned as follows: 0 = poor, 1 = fair, 2 = good, 3 = very good and 4 = excellent, as recorded by the subjects at the Day 14 site visit
Time Frame
14 days
Title
Change in WOMAC Stiffness subscale (Scale 0-8)
Description
The mean group change for OLT1177 Gel and vehicle control from Baseline (Day 0) to Day 7 in the WOMAC Stiffness subscale (Scale 0-8) and in the WOMAC Physical function subscale (Scale 0-68), which is determined by subjects responses to questions at the Day 7 site visit
Time Frame
7 days
Title
Change in WOMAC Stiffness subscale (Scale 0-8)
Description
The mean group change for OLT1177 Gel and vehicle control from Baseline (Day 0) to Day 14 in the WOMAC Stiffness subscale (Scale 0-8) and in the WOMAC Physical function subscale (Scale 0-68), which is determined by subjects responses to questions at the Day 14 site visit
Time Frame
14 days
Title
Change in the use of Rescue Medication
Description
The mean group change for OLT1177 Gel and vehicle control in the proportion of subjects who required the use of Rescue Medication
Time Frame
14 days
Title
Change in the time to use of Rescue Medication
Description
The mean group time to use of Rescue Medication for OLT1177 Gel and vehicle control after the first dose of Investigational Drug
Time Frame
14 days
Title
Proportion of subjects experiencing an improvement in WOMAC knee pain subscale
Description
The proportion of subjects who experience an improvement in WOMAC knee pain subscale (Scale 0-20, transformed to a 0 to 100 scale) from Baseline (Day 0) to Day 14 equal to or greater than the minimum clinically important improvement (MCII) threshold of 15-mm
Time Frame
14 days
Title
Proportion of subjects experiencing an improvement in WOMAC knee pain subscale
Description
The proportion of subjects who experience an improvement in WOMAC knee pain subscale (Scale 0-20, transformed to a 0 to 100 scale) from Baseline (Day 0) to Day 14 equal to or greater than the minimum clinically important improvement (MCII) threshold of 20%
Time Frame
14 days
Title
Proportion of subjects whose WOMAC knee pain subscale is less than the PASS
Description
The proportion of subjects whose WOMAC knee pain subscale (Scale 0-20, transformed to a 0 to 100 scale) at Day 14 is less than the patient acceptable symptom state (PASS) of 40
Time Frame
14 days
Title
Proportion of subjects experiencing an improvement in Pain on Movement
Description
The proportion of subjects who experience an improvement in Pain on Movement (100-mm VAS) from Baseline (Day 0) to Day 14 equal to or greater than the minimum clinically important improvement (MCII) threshold of 15-mm
Time Frame
14 days
Title
Proportion of subjects experiencing an improvement in Pain on Movement
Description
The proportion of subjects who experience an improvement in Pain on Movement (100-mm VAS) from Baseline (Day 0) to Day 14 equal to or greater than the minimum clinically important improvement (MCII) threshold of 20%
Time Frame
14 days
Title
Proportion of subjects whose POM is less than the PASS
Description
The proportion of subjects whose Pain on Movement (100-mm VAS) at Day 14 is less than the patient acceptable symptom state (PASS) of 40-mm
Time Frame
14 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 35 to 80
Subjects of childbearing potential and their partners must use effective contraception
OA based on the ACR criteria
OA of the knee ≥ 6 months prior to Screening
OA knee pain which required NSAID or other therapy for ≥ 15 days
Pain on Movement in the contralateral knee be ≤ 20 mm
Radiographic evidence of OA by Kellgren-Lawrence score of 2 or 3 taken 6 months prior to Screening
Moderate to severe OA pain defined as POM score between 50 mm and 90 mm
Baseline WOMAC pain subscale score ≥ 9
No change in physical activity and/or therapy for the past 3 months
Provide written informed consent and comply with the trial
Exclusion Criteria:
Use of Rescue Medication or any other pain medication 48 hours prior to Baseline visit
Inflammatory skin condition over the target knee
Extreme pain in the target knee characterized by POM score of > 90 mm
Mild pain in the target knee, characterized by POM score of < 50 mm
> 30 mm POM score variability in Days -2 to -1 from Baseline visit
Baseline POM score of > 20 mm for the contralateral knee or any other significant joint or general pain at Baseline visit
Excessive effusion in the target knee
Heat and/or redness in comparison to the contralateral knee
Knock-kneed or bow-legged defined by valgus or varus deformity of ≥ 15 degrees
Acute or chronic injury other than OA
Radiographic evidence of OA by Kellgren-Lawrence score of 0, 1 or 4
Open surgery of the target knee within the last year
Arthroscopic surgery of the target knee within the last 6 months
Surgery of the target knee requiring insertion of a medical device or surgical hardware
Use of prohibited concomitant medications/therapies during the 7-day washout period or planned use during the 14-day treatment period including:
Prescription medications to treat pain, OTC and natural supplements
Muscle relaxants unless on a stable dose ≥ 30 days prior to Screening
Nutraceuticals unless on a stable dose ≥ 3 months prior to Screening
Sedative hypnotics unless on a stable dose ≥ 30 days prior to Screening
Devices or therapeutic treatments for knee pain or ambulation
Systemic corticosteroids
Other Investigational Drugs
Chemotherapeutic drugs
Immunotherapy
Topical products applied to the target knee
Cyclosporine (except ophthalmic), lithium, methotrexate
Anti-depressants or medications acting on the central nervous system, unless on a stable dose for depression ≥ 3 months prior to Screening
Narcotics or previous history of chronic narcotic use
Rescue Medication within 48 hours of Baseline, Day 7 or Day 14 visits
Intraarticular steroids in the target knee within the previous 3 months or in any other joint within the previous 30 days
Intraarticular hyaluronate within the previous 6 months or in any other joint within the previous 30 days
Systemic corticosteroids within the prior month
Documented history of inflammatory joint disease
BMI over 35
Uncontrolled psychiatric conditions
Cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematological or neurological disease or prior surgery
Uncontrolled hypertension
Diabetes with an HbA1c level > 8
Known positive for HIV, Hepatitis B surface antigen (HBsAg) or antibodies to Hepatitis C Virus (HCV)
Cancer within the past 5 years, except for treated basal cell or squamous cell carcinoma of the skin
Any other medical conditions, diseases or prior surgeries
Interventional and/or surgical procedure during the 28 days following randomization
Change in level of physical activity during the 28 days following randomization
Active infection or fever ≥ 38°C within 3 days of Baseline visit
Known sensitivity to Investigational Drug
Women planning to become pregnant during the 28-day trial
Participation in any Investigational Drug or device trial within 30-day prior to Baseline visit
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jaime A. Pachon, MD
Organizational Affiliation
Miami Research Associates
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Bruce G. Rankin, D.O., C.P.I
Organizational Affiliation
Avail Clinical Research
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Treva W. Tyson, MD
Organizational Affiliation
Wake Research Associates
Official's Role
Principal Investigator
Facility Information:
Facility Name
Avail Clinical Research
City
DeLand
State/Province
Florida
ZIP/Postal Code
32720
Country
United States
Facility Name
Miami Research Associates
City
South Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
Wake Research Associates
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27612
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Phase 2 Efficacy Trial of OLT1177 Gel in Subjects With Moderate to Severe Pain Associated With OA of the Knee
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