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Osteoarthritis, HipPhase 2NCT02944448

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

A Phase 2 study testing CR845 tablet 1 mg, CR845 tablet 2.5 mg and CR845 tablet 5 mg in people with Osteoarthritis, Hip and Osteoarthritis, Knee, run by Cara Therapeutics, Inc. at 35 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 25 years and older
What is being tested?
CR845 tablet 1 mg, CR845 tablet 2.5 mg and CR845 tablet 5 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
761 participants
Where
35 sitesUnited States
Study dates
Sep 2016to Jun 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 25 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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).
  • If male, the patient must be surgically or biologically sterile. If not sterile, the patient must agree to use an acceptable form of birth control with a heterosexual partner (as described in inclusion criterion #9) or abstain from sexual relations during the treatment period and for 3 days following the last dose of study drug.
  • 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
  • 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).
  • If male, the patient must be surgically or biologically sterile. If not sterile, the patient must agree to use an acceptable form of birth control with a heterosexual partner (as described in inclusion criterion #9) or abstain from sexual relations during the treatment period and for 3 days following the last dose of study drug.
  • 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

Who cannot join

  • Has had a joint replacement in the index joint.
  • Has received an intra-articular injection of corticosteroids or hyaluronic acid in the index joint within 3 months prior to the Screening Visit.
  • Has started a new medication for chronic illness within 30 days prior to the Screening Visit.
  • Is receiving opioid analgesic treatment for OA of the hip or knee at a dose > 40 mg of morphine equivalent.
  • Uses antipsychotics, antiepileptics, sedatives, hypnotics, or antianxiety agents, selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants with a dose change <30 days prior to day 1 of the study.
  • Has a history or current diagnosis of substance dependence (except caffeine or nicotine) or alcohol abuse, according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).
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  • Has a positive urine drug screen for drugs of abuse at Screening.
  • Has been diagnosed with a condition of hyperhidrosis (excessive sweating) or primary hypodipsia (a reduced sense of thirst).
  • Has a history (within 6 months) of clinically meaningful orthostatic changes in vital signs OR, at Screening, has a decrease in systolic blood pressure by > 20 mm Hg or a decrease in diastolic blood pressure by 10 mm Hg together with an increase in heart rate of > 30 beats per minute when transitioning from supine to standing measurements.
  • Has a medical condition (e.g., a cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine [adrenal hyperplasia], immunologic, dermatologic, neurologic, oncologic, or psychiatric) or a significant laboratory abnormality that, in the Investigator's opinion, would jeopardize the safety of the patient or is likely to confound the study measurements.
  • Has had any gastric bypass surgery (for weight loss).
  • Has a corrected QT interval of >450 msec in males, >470 msec in females, or clinically significant abnormality on screening ECG.
  • Has a serum sodium level > 143 mmol/L at Screening.
  • Has impaired renal function indicated by serum creatinine > 2 × the reference upper limit of normal (ULN).
  • Has a serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 × the reference ULN, or total bilirubin > 2 × the ULN at Screening.
  • Has, in the opinion of the Investigator, any clinical signs of dehydration or hypovolemia (e.g., symptomatic hypotension) or associated laboratory abnormalities (e.g., elevated hematocrit or elevated blood urea nitrogen [BUN] > 1.5 × the reference ULN) at Screening.
  • Has taken opioid or non-opioid pain medication (e.g., nonsteroidal anti-inflammatory drugs [NSAIDs] such as naproxen or cyclooxygenase-2 inhibitors) within 5 days prior to study drug administration. Acetaminophen use is allowed. (Section 8.8)
  • Has received another investigational drug within 30 days prior to Baseline or has planned to participate in another clinical trial while enrolled in this study.

Trial locations and contacts

35 sites in 1 country.

35 sites in 1 country

United States35 sites
  • Cara Therapeutics Study Site

    Austin, Texas, 78731

  • Cara Therapeutics Study Site

    Berlin, New Jersey, 08009

  • Cara Therapeutics Study Site

    Binghamton, New York, 13901

  • Cara Therapeutics Study Site

    Birmingham, Alabama, 35216

  • Cara Therapeutics Study Site

    Carmichael, California, 95608

  • Cara Therapeutics Study Site

    Charleston, South Carolina, 29406

  • Cara Therapeutics Study Site

    Charleston, South Carolina, 29407

  • Cara Therapeutics Study Site

    Charlottesville, Virginia, 22911

  • Cara Therapeutics Study Site

    Cincinnati, Ohio, 45242

  • Cara Therapeutics Study Site

    Cincinnati, Ohio, 45246

  • Cara Therapeutics Study Site

    Dallas, Texas, 75234

  • Cara Therapeutics Study Site

    Duncansville, Pennsylvania, 16635

  • Cara Therapeutics Study Site

    Greenville, South Carolina, 29601

  • Cara Therapeutics Study Site

    Hazelwood, Missouri, 63042

  • Cara Therapeutics Study Site

    Homestead, Florida, 33030

  • Cara Therapeutics Study Site

    Jupiter, Florida, 33458

  • Cara Therapeutics Study Site

    Lake Worth, Florida, 33462

  • Cara Therapeutics Study Site

    Las Vegas, Nevada, 89144

  • Cara Therapeutics Study Site

    Miami, Florida, 33183

  • Cara Therapeutics Study Site

    Oklahoma City, Oklahoma, 73119

  • Cara Therapeutics Study Site

    Oldsmar, Florida, 34677

  • Cara Therapeutics Study Site

    Omaha, Nebraska, 68134

  • Cara Therapeutics Study Site

    Orlando, Florida, 32806

  • Cara Therapeutics Study Site

    Peoria, Arizona, 85351

  • Cara Therapeutics Study Site

    Phoenix, Arizona, 85023

  • Cara Therapeutics Study Site

    Plano, Texas, 75024

  • Cara Therapeutics Study Site

    Plano, Texas, 75075

  • Cara Therapeutics Study Site

    Plantation, Florida, 33317

  • Cara Therapeutics Study Site

    Rochester, New York, 14609

  • Cara Therapeutics Study Site

    San Antonio, Texas, 78209

  • Cara Therapeutics Study Site

    San Diego, California, 92123

  • Cara Therapeutics Study Site

    Savannah, Georgia, 31406

  • Cara Therapeutics Study Site

    South Miami, Florida, 33143

  • Cara Therapeutics Study Site

    Tampa, Florida, 33634

  • Cara Therapeutics Study Site

    Tustin, California, 92780

Other trials in United States

About this study

Official title: A 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. 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.

Read the detailed description

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.

Being tested
CR845 tablet 1 mg, CR845 tablet 2.5 mg, CR845 tablet 5 mg, Placebo tablet
Keywords
Osteoarthritis, Hip, Knee, CR845, Analgesic, Kappa opioid, difelikefalin
Medical subject headings
Osteoarthritis, Hip, Osteoarthritis, Knee, Arthritis, Joint Diseases, Musculoskeletal Diseases, Rheumatic Diseases, Osteoarthritis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CR845 tablet 1 mgDrug

    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 2.5 mgDrug

    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 5 mgDrug

    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 tabletDrug

    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.

Study groups in NCT02944448
Study groupRoleWhat they receive
CR845 tablet 1 mgActive comparatorDosing twice a day (BID) for a total of 8 weeks, with each dose administered at least 2 hours prior to or after a meal.
Receives: Drug: CR845 tablet 1 mg
CR845 tablet 2.5 mgActive comparatorDosing twice a day (BID) for a total of 8 weeks, with each dose administered at least 2 hours prior to or after a meal.
Receives: Drug: CR845 tablet 2.5 mg
CR845 tablet 5 mgActive comparatorDosing twice a day (BID) for a total of 8 weeks, with each dose administered at least 2 hours prior to or after a meal.
Receives: Drug: CR845 tablet 5 mg
Placebo tabletPlacebo comparatorDosing twice a day (BID) for a total of 8 weeks, with each dose administered at least 2 hours prior to or after a meal.
Receives: Drug: Placebo tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Baseline, Week 8

Secondary outcomes (9)
  1. 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).

    Measured: Baseline, Week 8

  2. 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.

    Measured: Baseline, Week 8

  3. 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.

    Measured: Baseline, Week 8

  4. 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.

    Measured: Baseline, Week 8

  5. 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.

    Measured: Week 8

  6. 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.

    Measured: Week 8

  7. 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".

    Measured: Week 8

  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.

    Measured: Week 8

  9. Proportion of Patients Withdrawing From Treatment Due to Lack of Analgesic Efficacy

    Measured: Week 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Oct 2016 (estimated)
  2. Study startSep 2016
  3. Primary completionMay 2017
  4. Study completionJun 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
761 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02944448
Sponsor's protocol ID
CR845-CLIN2002-PO
Status last verified
Oct 2020
First submitted
4 Oct 2016
Last updated
20 Oct 2020
Data monitoring committee
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CR845 tablet 1 mg, CR845 tablet 2.5 mg and CR845 tablet 5 mg in people with Osteoarthritis, Hip and Osteoarthritis, Knee, run by Cara Therapeutics, Inc. at 35 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 35 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). (time frame: Baseline, Week 8). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2020.

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