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

Phase 2

Completed

Conditions: Osteoarthritis of the Knee

Interventions: Drug: OLT1177 Gel
Other: Placebo gel

Registration Number: NCT01768975

Lead Sponsor: Olatec Therapeutics LLC

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 79

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
OLT1177 Gel	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
Placebo gel	Placebo gel	Identical dose and dosing regimen as the Investigational Drug (OLT1177 Gel)

Primary Outcome Measures

Name	Time	Method
Change in WOMAC knee pain subscale (scale 0 - 20)	14 days	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

Name	Time	Method
Change in the use of Rescue Medication	14 days	The mean group change for OLT1177 Gel and vehicle control in the proportion of subjects who required the use of Rescue Medication
Mean group rating of Relative Knee Pain (5-point scale)	50 minutes post dose (± 10 minutes)	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 the time to use of Rescue Medication	14 days	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 whose POM is less than the PASS	14 days	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
Change in WOMAC knee pain subscale	7 days	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 Global Rating of Disease	14 days	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 Current Knee Pain (100-mm VAS)	50 minutes post dose (± 10 minutes)	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
Change in Pain on Movement (100-mm VAS)	14 days	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
Proportion of subjects experiencing an improvement in WOMAC knee pain subscale	14 days	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	14 days	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	14 days	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%
Change in Global Evaluation of Treatment	14 days	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)	14 days	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

Trial Locations

Locations (3): Wake Research Associates
🇺🇸
Raleigh, North Carolina, United States
Avail Clinical Research
🇺🇸
DeLand, Florida, United States
Miami Research Associates
🇺🇸
South Miami, Florida, United States