Phase 2 Efficacy Trial of OLT1177 Gel in Subjects With Moderate to Severe Pain Associated With OA of the Knee

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Olatec Industries LLC
ClinicalTrials.gov Identifier:
NCT01768975
First received: January 14, 2013
Last updated: September 25, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Osteoarthritis of the Knee
Drug: OLT1177 Gel
Other: Placebo gel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Olatec Industries LLC:

Primary Outcome Measures:
  • Change in WOMAC knee pain subscale (scale 0 - 20) [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    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) [ Time Frame: 50 minutes post dose (± 10 minutes) ] [ Designated as safety issue: No ]
    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) [ Time Frame: 50 minutes post dose (± 10 minutes) ] [ Designated as safety issue: No ]
    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 [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    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) [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    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) [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    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) [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    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) [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    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


Enrollment: 79
Study Start Date: January 2013
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: OLT1177 Gel
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
Drug: OLT1177 Gel
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
Other Name: OLT1177
Placebo Comparator: Placebo gel
Identical dose and dosing regimen as the Investigational Drug (OLT1177 Gel)
Other: Placebo gel
Identical dose and dosing regimen as the Investigational Drug (OLT1177 Gel)

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.

  Eligibility

Ages Eligible for Study:   35 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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:

    1. Prescription medications to treat pain, OTC and natural supplements
    2. Muscle relaxants unless on a stable dose ≥ 30 days prior to Screening
    3. Nutraceuticals unless on a stable dose ≥ 3 months prior to Screening
    4. Sedative hypnotics unless on a stable dose ≥ 30 days prior to Screening
    5. Devices or therapeutic treatments for knee pain or ambulation
    6. Systemic corticosteroids
    7. Other Investigational Drugs
    8. Chemotherapeutic drugs
    9. Immunotherapy
    10. Topical products applied to the target knee
    11. Cyclosporine (except ophthalmic), lithium, methotrexate
    12. Anti-depressants or medications acting on the central nervous system, unless on a stable dose for depression ≥ 3 months prior to Screening
    13. Narcotics or previous history of chronic narcotic use
    14. 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01768975

Locations
United States, Florida
Avail Clinical Research
DeLand, Florida, United States, 32720
Miami Research Associates
South Miami, Florida, United States, 33143
United States, North Carolina
Wake Research Associates
Raleigh, North Carolina, United States, 27612
Sponsors and Collaborators
Olatec Industries LLC
Investigators
Principal Investigator: Jaime A. Pachon, MD Miami Research Associates
Principal Investigator: Bruce G. Rankin, D.O., C.P.I Avail Clinical Research
Principal Investigator: Treva W. Tyson, MD Wake Research Associates
  More Information

No publications provided

Responsible Party: Olatec Industries LLC
ClinicalTrials.gov Identifier: NCT01768975     History of Changes
Other Study ID Numbers: OLT1177-02
Study First Received: January 14, 2013
Last Updated: September 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Olatec Industries LLC:
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

Additional relevant MeSH terms:
Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases

ClinicalTrials.gov processed this record on October 29, 2014