A Study Evaluating Pain Relief and Safety of Orally Administered CR845 in Patients With Osteoarthritis of Hip or Knee

NCT02944448 | Completed Phase 2 Results

• 1 other identifier: CR845-CLIN2002-PO
• Study Type: interventional
• Target: 761
• Locations: 1 country
• Sites: 35

Brief Summary

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.

Conditions

Osteoarthritis, Hip; Osteoarthritis, Knee; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Keywords

Osteoarthritis; Hip; Knee; CR845; Analgesic; Kappa opioid; difelikefalin

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline, Week 8

Secondary Outcomes (9)

• Change From Baseline in the Western Ontario & McMaster Osteoarthritis (WOMAC) Index Total Score at Week 8

  Baseline, Week 8

• Change From Baseline in the WOMAC Pain Intensity Sub-scale Score at Week 8

  Baseline, Week 8

• Change From Baseline in the WOMAC Stiffness Sub-scale Score at Week 8

  Baseline, Week 8

• Change From Baseline in the WOMAC Function Sub-scale Score at Week 8

  Baseline, Week 8

• Proportion of Patients With at Least 30% Improvement From Baseline in the Weekly Mean Pain Intensity at Week 8

  Week 8

Study Arms (4)

CR845 tablet 1 mg

ACTIVE COMPARATOR

Dosing twice a day (BID) for a total of 8 weeks, with each dose administered at least 2 hours prior to or after a meal.

Drug: CR845 tablet 1 mg

CR845 tablet 2.5 mg

ACTIVE COMPARATOR

Dosing twice a day (BID) for a total of 8 weeks, with each dose administered at least 2 hours prior to or after a meal.

Drug: CR845 tablet 2.5 mg

CR845 tablet 5 mg

ACTIVE COMPARATOR

Dosing twice a day (BID) for a total of 8 weeks, with each dose administered at least 2 hours prior to or after a meal.

Drug: CR845 tablet 5 mg

Placebo tablet

PLACEBO COMPARATOR

Dosing twice a day (BID) for a total of 8 weeks, with each dose administered at least 2 hours prior to or after a meal.

Drug: Placebo tablet

Interventions

CR845 tablet 1 mg DRUG

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 tablet 1 mg

CR845 tablet 2.5 mg DRUG

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 tablet 2.5 mg

CR845 tablet 5 mg DRUG

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.

CR845 tablet 5 mg

Placebo tablet DRUG

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.

Placebo tablet

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily provides written informed consent to participate in the study prior to any study procedures.
• Is able to speak, read, and communicate clearly in English or Spanish; is able to understand the study procedures.
• Male or female ≥ 25 years of age.
• Body mass index (BMI) ≤ 40 kg/m2.
• Has OA of the hip or knee according to American College of Rheumatology (ACR) criteria.
• Reports an average pain intensity level ≥ 5 in the index joint at Screening on a 0-10 NRS scale.
• Is either opioid-naïve (defined as taking \< 10 mg a day of morphine equivalent 14 days prior to screening) or opioid-experienced. If receiving opioid analgesic medication for OA, patients must be on a stable dose ≤ 40 mg of morphine equivalents for 14 days prior to screening.
• Willing to discontinue currently used pain medications beginning 5 days prior to the Baseline Visit and throughout the study. Acetaminophen use is allowed. (Section 8.8)
• If female:
• Of childbearing potential - the patient must be willing to practice an acceptable form of birth control (defined as the use of an intrauterine device, a barrier method with spermicide, condoms, any form of hormonal contraceptives, or abstinence from sexual intercourse) for the duration of treatment and for at least 3 days following the last dose of study drug.
• Of non-childbearing potential - the patient must be surgically or biologically sterile (hysterectomy, bilateral oophorectomy, bilateral tubal ligation, or postmenopausal for at least 1 year).
• Is free of other physical, mental, or medical conditions that, in the opinion of the Investigator, would make study participation inadvisable.
• Reports a daily pain intensity score in the index joint ≥ 5 (on a 0-10 NRS scale) during 4 or more of the last 7 days prior to randomization, with 2 consecutive days ≥ 5 occurring just prior to randomization

You may not qualify if:

• A patient will be eligible for enrollment if the following criteria are met:
• Voluntarily provides written informed consent to participate in the study prior to any study procedures.
• Is able to speak, read, and communicate clearly in English or Spanish; is able to understand the study procedures.
• Male or female ≥ 25 years of age.
• Body mass index (BMI) ≤ 40 kg/m2.
• Has OA of the hip or knee according to American College of Rheumatology (ACR) criteria.
• Reports an average pain intensity level ≥ 5 in the index joint at Screening on a 0-10 NRS scale.
• Is either opioid-naïve (defined as taking \< 10 mg a day of morphine equivalent 14 days prior to screening) or opioid-experienced. If receiving opioid analgesic medication for OA, patients must be on a stable dose ≤ 40 mg of morphine equivalents for 14 days prior to screening.
• Willing to discontinue currently used pain medications beginning 5 days prior to the Baseline Visit and throughout the study. Acetaminophen use is allowed. (Section 8.8)
• If female:
• Of childbearing potential - the patient must be willing to practice an acceptable form of birth control (defined as the use of an intrauterine device, a barrier method with spermicide, condoms, any form of hormonal contraceptives, or abstinence from sexual intercourse) for the duration of treatment and for at least 3 days following the last dose of study drug.
• Of non-childbearing potential - the patient must be surgically or biologically sterile (hysterectomy, bilateral oophorectomy, bilateral tubal ligation, or postmenopausal for at least 1 year).
• Is free of other physical, mental, or medical conditions that, in the opinion of the Investigator, would make study participation inadvisable.
• Reports a daily pain intensity score in the index joint ≥ 5 (on a 0-10 NRS scale) during 4 or more of the last 7 days prior to randomization, with 2 consecutive days ≥ 5 occurring just prior to randomization
• Has had a joint replacement in the index joint.

Sponsors & Collaborators

• Cara Therapeutics, Inc.: lead

Study Sites (35)

Cara Therapeutics Study Site

Birmingham, Alabama, 35216, United States

Location

Cara Therapeutics Study Site

Peoria, Arizona, 85351, United States

Location

Cara Therapeutics Study Site

Phoenix, Arizona, 85023, United States

Location

Cara Therapeutics Study Site

Carmichael, California, 95608, United States

Location

Cara Therapeutics Study Site

San Diego, California, 92123, United States

Location

Cara Therapeutics Study Site

Tustin, California, 92780, United States

Location

Cara Therapeutics Study Site

Homestead, Florida, 33030, United States

Location

Cara Therapeutics Study Site

Jupiter, Florida, 33458, United States

Location

Cara Therapeutics Study Site

Lake Worth, Florida, 33462, United States

Location

Cara Therapeutics Study Site

Miami, Florida, 33183, United States

Location

Cara Therapeutics Study Site

Oldsmar, Florida, 34677, United States

Location

Cara Therapeutics Study Site

Orlando, Florida, 32806, United States

Location

Cara Therapeutics Study Site

Plantation, Florida, 33317, United States

Location

Cara Therapeutics Study Site

South Miami, Florida, 33143, United States

Location

Cara Therapeutics Study Site

Tampa, Florida, 33634, United States

Location

Cara Therapeutics Study Site

Savannah, Georgia, 31406, United States

Location

Cara Therapeutics Study Site

Hazelwood, Missouri, 63042, United States

Location

Cara Therapeutics Study Site

Omaha, Nebraska, 68134, United States

Location

Cara Therapeutics Study Site

Las Vegas, Nevada, 89144, United States

Location

Cara Therapeutics Study Site

Berlin, New Jersey, 08009, United States

Location

Cara Therapeutics Study Site

Binghamton, New York, 13901, United States

Location

Cara Therapeutics Study Site

Rochester, New York, 14609, United States

Location

Cara Therapeutics Study Site

Cincinnati, Ohio, 45242, United States

Location

Cara Therapeutics Study Site

Cincinnati, Ohio, 45246, United States

Location

Cara Therapeutics Study Site

Oklahoma City, Oklahoma, 73119, United States

Location

Cara Therapeutics Study Site

Duncansville, Pennsylvania, 16635, United States

Location

Cara Therapeutics Study Site

Charleston, South Carolina, 29406, United States

Location

Cara Therapeutics Study Site

Charleston, South Carolina, 29407, United States

Location

Cara Therapeutics Study Site

Greenville, South Carolina, 29601, United States

Location

Cara Therapeutics Study Site

Austin, Texas, 78731, United States

Location

Cara Therapeutics Study Site

Dallas, Texas, 75234, United States

Location

Cara Therapeutics Study Site

Plano, Texas, 75024, United States

Location

Cara Therapeutics Study Site

Plano, Texas, 75075, United States

Location

Cara Therapeutics Study Site

San Antonio, Texas, 78209, United States

Location

Cara Therapeutics Study Site

Charlottesville, Virginia, 22911, United States

Location

MeSH Terms

Conditions

Osteoarthritis, Hip; Osteoarthritis, Knee; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Osteoarthritis

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Frédérique Menzaghi, PhD
• Organization: Cara Therapeutics

clinicaltrials.gov@caratherapeutics.com

203-406-3700

Study Officials

• Joseph Stauffer, DO, MBA

  Cara Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2016
• First Posted: October 25, 2016
• Study Start: September 1, 2016
• Primary Completion: May 1, 2017
• Study Completion: June 1, 2017
• Last Updated: October 20, 2020
• Results First Posted: October 20, 2020

Record last verified: 2020-10

Locations

US (35)