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

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.

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 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