The study schedule consists of a Screening Period (up to 14 days), a blinded 4- week Titration-to-Effect Period with weekly visits, a blinded 4-week Maintenance Treatment Period at the optimal dose level determined for each patient, and a 1-week Follow-up Period. Eligible patients will be randomized to receive either CR845 or placebo in a 2:1 ratio. Every patient will be started on a 1-mg dose of CR845 or matching placebo. During the post-randomization Titration-to-Effect period, the dose of study drug may be increased to 2.5 mg or 5 mg in a double-blind fashion. Patients may know their dose is being changed but will not know whether they were randomization to active study drug or placebo. Approximately 330 patients will be enrolled in this study.
This is a multicenter, randomized, double-blind, placebo-controlled, titration-to-effect study of orally administered CR845 in patients with osteoarthritis of the hip or knee. The study schedule consists of a Screening Period (up to 14 days), a blinded 4- week Titration-to-Effect Period with weekly visits, a blinded 4-week Maintenance Treatment Period at the optimal dose level determined for each patient, and a 1-week Follow-up Period. Eligible patients will be randomized to receive either CR845 or placebo in a 2:1 ratio. Randomization will be stratified based on a patient's primary OA joint (knee vs. hip). Every patient will be started on a 1-mg dose of CR845 or matching placebo. During the post-randomization Titration-to-Effect period, the dose of study drug may be increased to 2.5 mg or 5 mg in a double-blind fashion. Patients may know their dose is being changed but will not know whether they were randomized to active study drug or placebo. Approximately 330 patients will be enrolled in this study. During the Screening, Titration-to-Effect and Follow-up Period, pain intensity scores will be obtained at specified time points. Blood sampling and safety assessments will be conducted during this period as well. The use of rescue medication for the treatment of any pain (including but not limited to headache, menstrual cramps, or non-target joint pain) during the study will be discussed with the patients at the Screening Visit. Acetaminophen is the only allowable rescue medication for pain beginning from Day -5 until the end of the Maintenance Treatment Period. Starting at the Screening Visit Acetaminophen will be provided as 325-mg tablets and its use (number of tablets taken in the previous 24 hours) will be reported each evening in the patient diary.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
761
CR845 tablets will be provided as 1 mg enteric-coated tablets. All tablets are white in color with no markings and are identical in appearance, regardless of dose and treatment.
CR845 tablets will be provided as 2.5 mg enteric-coated tablets. All tablets are white in color with no markings and are identical in appearance, regardless of dose and treatment.
CR845 tablets will be provided as 5 mg enteric-coated tablets. All tablets are white in color with no markings and are identical in appearance, regardless of dose and treatment.
Placebo tablets will be provided as enteric-coated tablets. All tablets are white in color with no markings and are identical in appearance, regardless of dose and treatment.
Cara Therapeutics Study Site
Birmingham, Alabama, United States
Cara Therapeutics Study Site
Peoria, Arizona, United States
Cara Therapeutics Study Site
Phoenix, Arizona, United States
Cara Therapeutics Study Site
Carmichael, California, United States
Cara Therapeutics Study Site
San Diego, California, United States
Change From Baseline at Week 8 With Respect to the Weekly Mean of the Daily 24-hour Pain Intensity for the Index Joint as Measured by the Numeric Rating Scale (NRS).
11-point NRS scale where 0 = no pain, and 10= pain as bad as you can imagine
Time frame: Baseline, Week 8
Change From Baseline in the Western Ontario & McMaster Osteoarthritis (WOMAC) Index Total Score at Week 8
The WOMAC Index is a self-administered assessment used to measure pain, stiffness, and physical function in patients with osteoarthritis. The WOMAC Index contains 24 questions across 3 different sub-scales (pain, stiffness, and function) all with scoring 0-10 (0 = No Pain/Stiffness/Difficulty, 10 = Extreme Pain/Stiffness/Difficulty). Each WOMAC Index Subscale score (Pain/Stiffness/Function) is calculated as the sum of all scores within that subscale. The pain subscale consists of five scores from 0-10, 0 is no pain 10 is extreme pain possible for a range of 0 - 50 points. The stiffness subscale consists of two scores from 0-10, 0 is no stiffness 10 is extreme stiffness possible for a range of 0 - 20 points. The function subscale consists of 17 scores from 0-10, 0 is no difficulty and 10 is extreme difficulty, for a range of 0 - 170 points. The WOMAC Index Total Score is calculated as the sum of all 24 scores (range of 0-240).
Time frame: Baseline, Week 8
Change From Baseline in the WOMAC Pain Intensity Sub-scale Score at Week 8
The pain subscale consists of five scores from 0-10, 0 is no pain 10 is extreme pain possible for a range of 0 - 50 points.
Time frame: Baseline, Week 8
Change From Baseline in the WOMAC Stiffness Sub-scale Score at Week 8
The stiffness subscale consists of two scores from 0-10, 0 is no stiffness 10 is extreme stiffness possible for a range of 0 - 20 points.
Time frame: Baseline, Week 8
Change From Baseline in the WOMAC Function Sub-scale Score at Week 8
The function subscale consists of 17 scores from 0-10, 0 is no difficulty and 10 is extreme difficulty, for a range of 0 - 170 points.
Time frame: Baseline, Week 8
Proportion of Patients With at Least 30% Improvement From Baseline in the Weekly Mean Pain Intensity at Week 8
A patient's pain response to treatment is defined as the percent improvement from baseline with respect to the weekly mean of "average pain in the last 24 hours" pain score during the last week of the Maintenance Treatment Period (Week 8) . If a patient's mean weekly pain score during the last week of the Maintenance Treatment Period is greater than the baseline score (i.e., the patient has an increase in pain compared to baseline), his/her response to treatment will be assigned a value of 0 (i.e. the patient will be considered a non-responder). Patients who discontinue study drug early will be considered non-responders to treatment and will be assigned a pain response of 0. The percentage of subjects achieving levels of treatment response 10% to 100% by 10% increments as defined above will be calculated with 30% of key interest as it has been shown to represent a clinically important improvement in pain.
Time frame: Week 8
Proportion of Patients With at Least 50% Improvement From Baseline in the Weekly Mean Pain Intensity at Week 8
A patient's pain response to treatment is defined as the percent improvement from baseline with respect to the weekly mean of "average pain in the last 24 hours" pain score during the last week of the Maintenance Treatment Period (Week 8) . If a patient's mean weekly pain score during the last week of the Maintenance Treatment Period is greater than the baseline score (i.e., the patient has an increase in pain compared to baseline), his/her response to treatment will be assigned a value of 0 (i.e. the patient will be considered a non-responder). Patients who discontinue study drug early will be considered non-responders to treatment and will be assigned a pain response of 0. The percentage of subjects achieving levels of treatment response 10% to 100% by 10% increments as defined above will be calculated with 30% of key interest as it has been shown to represent a clinically important improvement in pain.
Time frame: Week 8
Proportion of Patients Whose OA Pain Was "Very Much Improved" or "Much Improved" as Indicated by Patient Global Impression of Change (PGIC) Score at Week 8
The PGIC is a self-administered instrument that measures the patient's overall impression of his/her OA on a 7-point scale where 1 = "Very much improved" and 7 = "Very much worse".
Time frame: Week 8
Average Daily Number of Acetaminophen Tablets Used During Entire Study
The average daily number of acetaminophen tablets used during the study will be calculated using data recorded in the patient diary as the sum of the total number of tablets used divided by the length of exposure (in days). The supplemental pain medication for OA will be grouped categorically into the following classes: (1) no supplemental acetaminophen tablets, (2) 0 to ≤ 0.5 tablets, (3) \> 0.5 to ≤ 1.0 tablets, (4) \> 1.0 to ≤ 2.0 tablets, and (5) \> 2.0 tablets.
Time frame: Week 8
Proportion of Patients Withdrawing From Treatment Due to Lack of Analgesic Efficacy
Time frame: Week 8
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Cara Therapeutics Study Site
Tustin, California, United States
Cara Therapeutics Study Site
Homestead, Florida, United States
Cara Therapeutics Study Site
Jupiter, Florida, United States
Cara Therapeutics Study Site
Lake Worth, Florida, United States
Cara Therapeutics Study Site
Miami, Florida, United States
...and 25 more locations