OsteoarthritisPhase 2NCT02524197
A Study of the Safety and Effectiveness of Orally Administered CR845 in Patients With Osteoarthritis of the Hip or Knee
A Phase 2 study testing CR845 0.25 mg, CR845 0.50 mg and CR845 1 mg in people with Osteoarthritis, run by Cara Therapeutics, Inc. at 5 sites in United States.
Trial summary
To assess the safety and tolerability of orally-administered CR845 in patients with osteoarthritis (OA) of the hip or knee. The study drug is being tested to reduce OA pain, and will be taken twice a day for two weeks, with four different doses (strengths) being tested. Read more about this study
- Who is it for?
- Ages 25 years and older
- Conditions the study is for
- Osteoarthritis
- What is being tested?
- CR845 0.25 mg, CR845 0.50 mg and CR845 1 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- 5 sitesUnited States
- Study dates
- Aug 2015to Jan 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- 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.
- BMI ≤ 40
- Has OA of the hip or knee according to American College of Rheumatology (ACR) criteria.
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- Reports an average pain intensity level ≥ 4 in the index joint at Screening on an NRS.
- Willing to discontinue currently used pain medications beginning 5 days prior to the Baseline Visit and throughout the study.
- 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 #8) 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, which, in the opinion of the Investigator, would make study participation inadvisable.
- Reports average daily pain intensity ≥ 4 in the index joint during the 3 days prior to Baseline on the NRS.
Who cannot join
- A patient will be excluded from enrollment if the patient meets any of the following criteria:
- 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.
- 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).
- Has a positive urine drug screen for drugs of abuse at Screening or Baseline.
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- Has been diagnosed with a condition of hyperhidrosis or primary hypodipsia.
- 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 condition) 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 a serum sodium level > 145 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.
- 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
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Altoona Center for Clinical Research
Duncansville, Pennsylvania, 16635
Triad Clinical Trials, LLC
Greensboro, North Carolina, 27410
Matthew Barton, MD
Las Vegas, Nevada
Heartland Clinical Research
Omaha, Nebraska, 68134
Clinical Investgations of Texas
Plano, Texas, 75075
About this study
Official title: A Single-Blind, Multiple Ascending-Dose Pilot Study of the Safety, Tolerability, Pharmacokinetics, and Effectiveness of Orally Administered CR845 in Patients With Osteoarthritis of the Hip or Knee
To assess the safety and tolerability of orally-administered CR845 in patients with osteoarthritis (OA) of the hip or knee. The study drug is being tested to reduce OA pain, and will be taken twice a day for two weeks, with four different doses (strengths) being tested. From screening period to follow up examination, the study is expected to last for up to 38 days per participant.
Read the detailed description
The purpose of this clinical study is to collect information on the effectiveness of CR845 and to look at the safety of different dose levels of CR845 tablets. Oral CR845 has been tested in healthy people. This is the first time that oral CR845 is being tested in patients with osteoarthritis.
Four different doses of CR845 will be tested in this study. Participants will be assigned to one of the four treatment groups. The first 6 participants in each of the 4 treatment groups will be given the study drug in an inpatient study unit (clinic) for approximately 2 days. Frequent blood samples will be taken to measure drug levels during these 2 days. Also, because the study drug (CR845) is known to increase urination during the first day, the amount of fluid that participants drink and the amount of urine that they void during the first day will also be measured.
At the end of the second day, a member of the clinical staff will check vital signs and the patient's laboratory results prior to discharge from the clinic. After that, the remainder of the treatment period is as an outpatient (at home). This involves taking an additional two tablets twice a day, and maintaining a diary that will be returned to the clinic upon completion.
- Conditions
- Osteoarthritis
- Being tested
- CR845 0.25 mg, CR845 0.50 mg, CR845 1 mg, CR845 5 mg
- Keywords
- Hip, Knee, Arthritis, pain, CR845, kappa opioid
- Medical subject headings
- Osteoarthritis, Arthritis, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CR845 0.25 mgDrug
Subjects will dose orally twice a day with CR845 0.25 mg tablets for two weeks. A diary will be kept for recording the individual's pain scores and dosing accountability.
CR845 0.50 mgDrug
Subjects will dose orally twice a day with CR845 0.50 mg tablets for two weeks. A diary will be kept for recording the individual's pain scores and dosing accountability.
CR845 1 mgDrug
Subjects will dose orally twice a day with CR845 1 mg tablets for two weeks. A diary will be kept for recording the individual's pain scores and dosing accountability.
CR845 5 mgDrug
Subjects will dose orally twice a day with CR845 5 mg tablets for two weeks. A diary will be kept for recording the individual's pain scores and dosing accountability.
| Study group | Role | What they receive |
|---|---|---|
| CR845 0.25 mg | Active comparator | Study medication will be taken b.i.d., in the morning (at least 2 hours before breakfast) and later in the afternoon (at least 2 hours before dinner), beginning on the morning of Day1 at the Baseline Visit.
Analgesic rescue medication (Acetaminophen) for the treatment of pain will be provided at the Screening Visit.
Patients will record their daily intake of study medication on the diary provided. Receives: Drug: CR845 0.25 mg |
| CR845 0.50 mg | Active comparator | Study medication will be taken b.i.d., in the morning (at least 2 hours before breakfast) and later in the afternoon (at least 2 hours before dinner), beginning on the morning of Day1 at the Baseline Visit.
Analgesic rescue medication (Acetaminophen) for the treatment of pain will be provided at the Screening Visit.
Patients will record their daily intake of study medication on the diary provided. Receives: Drug: CR845 0.50 mg |
| CR845 1 mg | Active comparator | Study medication will be taken b.i.d., in the morning (at least 2 hours before breakfast) and later in the afternoon (at least 2 hours before dinner), beginning on the morning of Day1 at the Baseline Visit.
Analgesic rescue medication (Acetaminophen) for the treatment of pain will be provided at the Screening Visit.
Patients will record their daily intake of study medication on the diary provided. Receives: Drug: CR845 1 mg |
| CR845 5 mg | Active comparator | Study medication will be taken b.i.d., in the morning (at least 2 hours before breakfast) and later in the afternoon (at least 2 hours before dinner), beginning on the morning of Day1 at the Baseline Visit.
Analgesic rescue medication (Acetaminophen) for the treatment of pain will be provided at the Screening Visit.
Patients will record their daily intake of study medication on the diary provided. Receives: Drug: CR845 5 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the Safety and Tolerability of orally-administered CR845 in patients with osteoarthritis of the hip or the knee, in sequentially escalating doses (0.25 mg, 0.50 mg, 1 mg and 5 mg).
The sentinel group will be dosed and monitored in an inpatient clinic unit for 48 hours, then discharged to complete remainder of treatment at home. Following the evaluation of the first group's safety data, the remaining cohorts will begin enrolling. The safety and tolerability of CR845 will be assessed by physical examination, monitoring of adverse events, vital signs, laboratory evaluations, and fluid balance.
Measured: Sentinel cohort initial 48 hours, all subjects 38 days
Secondary outcomes (2)
To characterize the pharmacokinetic (pk) profile of orally-administered CR845 with twice a day (b.i.d) dosing
The pharmacokinetic variables for the sentinel groups will have their plasma concentrations summarized and compared to pre-dosing.
Measured: 48 hours
To explore the effectiveness of orally administered CR845 in this patient population
The effectiveness of CR845 will be assessed by the measurement of daily joint pain intensity scores (numeric rating scale [NRS]) over time, the impact of treatment on pain, function and stiffness (Western Ontario and McMaster Osteoarthritis Index [WOMAC] and global assessment of OA following treatment (Patient Global Assessment [PGA]).
Measured: 38 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2015 (estimated)
- Study startAug 2015
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OsteoarthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Single blind
- Who is masked
- Participant
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cara Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Paul Tiseo, PhD, Study director, Cara Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02524197
- Sponsor's protocol ID
- CR845-CLIN2001-PO
- Status last verified
- Jan 2017
- First submitted
- 12 Aug 2015
- Last updated
- 31 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-Blind, Multiple Ascending-Dose Pilot Study of the Safety, Tolerability, Pharmacokinetics, and Effectiveness of Orally Administered CR845 in Patients With Osteoarthritis of the Hip or Knee
- ClinicalTrials.gov ID
- NCT02524197
- Acronym / sponsor ID
- CR845-CLIN2001-PO
- Conditions
- Osteoarthritis
- Keywords
- Hip, Knee, Arthritis, pain, CR845, kappa opioid
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Cara Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- Aug 2015
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 14 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To assess the safety and tolerability of orally-administered CR845 in patients with osteoarthritis (OA) of the hip or knee. The study drug is being tested to reduce OA pain, and will be taken twice a day for two weeks, with four different doses (strengths) being tested. From screening period to follow up examination, the study is expected to last for up to 38 days per participant.
Detailed description
The purpose of this clinical study is to collect information on the effectiveness of CR845 and to look at the safety of different dose levels of CR845 tablets. Oral CR845 has been tested in healthy people. This is the first time that oral CR845 is being tested in patients with osteoarthritis.
Four different doses of CR845 will be tested in this study. Participants will be assigned to one of the four treatment groups. The first 6 participants in each of the 4 treatment groups will be given the study drug in an inpatient study unit (clinic) for approximately 2 days. Frequent blood samples will be taken to measure drug levels during these 2 days. Also, because the study drug (CR845) is known to increase urination during the first day, the amount of fluid that participants drink and the amount of urine that they void during the first day will also be measured.
At the end of the second day, a member of the clinical staff will check vital signs and the patient's laboratory results prior to discharge from the clinic. After that, the remainder of the treatment period is as an outpatient (at home). This involves taking an additional two tablets twice a day, and maintaining a diary that will be returned to the clinic upon completion.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| CR845 0.25 mg | Active comparator | Drug: CR845 0.25 mgStudy medication will be taken b.i.d., in the morning (at least 2 hours before breakfast) and later in the afternoon (at least 2 hours before dinner), beginning on the morning of Day1 at the Baseline Visit. Analgesic rescue medication (Acetaminophen) for the treatment of pain will be provided at the Screening Visit. Patients will record their daily intake of study medication on the diary provided. |
| CR845 0.50 mg | Active comparator | Drug: CR845 0.50 mgStudy medication will be taken b.i.d., in the morning (at least 2 hours before breakfast) and later in the afternoon (at least 2 hours before dinner), beginning on the morning of Day1 at the Baseline Visit. Analgesic rescue medication (Acetaminophen) for the treatment of pain will be provided at the Screening Visit. Patients will record their daily intake of study medication on the diary provided. |
| CR845 1 mg | Active comparator | Drug: CR845 1 mgStudy medication will be taken b.i.d., in the morning (at least 2 hours before breakfast) and later in the afternoon (at least 2 hours before dinner), beginning on the morning of Day1 at the Baseline Visit. Analgesic rescue medication (Acetaminophen) for the treatment of pain will be provided at the Screening Visit. Patients will record their daily intake of study medication on the diary provided. |
| CR845 5 mg | Active comparator | Drug: CR845 5 mgStudy medication will be taken b.i.d., in the morning (at least 2 hours before breakfast) and later in the afternoon (at least 2 hours before dinner), beginning on the morning of Day1 at the Baseline Visit. Analgesic rescue medication (Acetaminophen) for the treatment of pain will be provided at the Screening Visit. Patients will record their daily intake of study medication on the diary provided. |
Who may qualify
- Ages
- 25 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
- BMI ≤ 40
- Has OA of the hip or knee according to American College of Rheumatology (ACR) criteria.
Key exclusion criteria (15 listed)
- A patient will be excluded from enrollment if the patient meets any of the following criteria:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CR845 0.25 mgSubjects will dose orally twice a day with CR845 0.25 mg tablets for two weeks. A diary will be kept for recording the individual's pain scores and dosing accountability. | Drug | CR845 0.25 mg |
| CR845 0.50 mgSubjects will dose orally twice a day with CR845 0.50 mg tablets for two weeks. A diary will be kept for recording the individual's pain scores and dosing accountability. | Drug | CR845 0.50 mg |
| CR845 1 mgSubjects will dose orally twice a day with CR845 1 mg tablets for two weeks. A diary will be kept for recording the individual's pain scores and dosing accountability. | Drug | CR845 1 mg |
| CR845 5 mgSubjects will dose orally twice a day with CR845 5 mg tablets for two weeks. A diary will be kept for recording the individual's pain scores and dosing accountability. | Drug | CR845 5 mg |
Primary outcome
To assess the Safety and Tolerability of orally-administered CR845 in patients with osteoarthritis of the hip or the knee, in sequentially escalating doses (0.25 mg, 0.50 mg, 1 mg and 5 mg).
Time frame: Sentinel cohort initial 48 hours, all subjects 38 days
The sentinel group will be dosed and monitored in an inpatient clinic unit for 48 hours, then discharged to complete remainder of treatment at home. Following the evaluation of the first group's safety data, the remaining cohorts will begin enrolling. The safety and tolerability of CR845 will be assessed by physical examination, monitoring of adverse events, vital signs, laboratory evaluations, and fluid balance.
2 secondary outcomes
To characterize the pharmacokinetic (pk) profile of orally-administered CR845 with twice a day (b.i.d) dosing
Time frame: 48 hours
To explore the effectiveness of orally administered CR845 in this patient population
Time frame: 38 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Tiseo, PhD study director
Cara Therapeutics
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CR845 0.25 mg, CR845 0.50 mg and CR845 1 mg in people with Osteoarthritis, run by Cara Therapeutics, Inc. at 5 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 14 inclusion and 15 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 31 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To assess the Safety and Tolerability of orally-administered CR845 in patients with osteoarthritis of the hip or the knee, in sequentially escalating doses (0.25 mg, 0.50 mg, 1 mg and 5 mg). (time frame: Sentinel cohort initial 48 hours, all subjects 38 days). 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 31 Jan 2017.