Postoperative PainPhase 2NCT01361568
Study to Evaluate Analgesic Effect of IV Administration of Kappa Agonist CR845 For Hysterectomy Surgery
A Phase 2 study testing CR845 in people with Postoperative Pain, run by Cara Therapeutics, Inc. at 18 sites in United States.
Trial summary
The primary purpose of this study is to determine if CR845 is effective in treating the pain associated with a laparoscopic hysterectomy. Read more about this study
- Who is it for?
- Ages 21 to 65 years, women only
- Conditions the study is for
- Postoperative Pain
- What is being tested?
- CR845
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 203 participants
- Where
- 18 sitesUnited States
- Study dates
- Jul 2011to Apr 2012
- 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 21 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to provide written informed consent prior to any study procedures;
- Able to communicate clearly with the Investigator and staff;
- Female between 21 and 65 years of age, inclusive;
- Scheduled for elective laparoscopic hysterectomy under general anesthesia;
- Negative result on serum pregnancy test at screening and negative urine pregnancy test at Baseline (for women of child-bearing potential only) and not currently breast feeding, or planning to do so within 30 days of dosing;
- Negative urine drug screen for drugs of abuse at Screening and at Baseline;
- American Society of Anesthesiologists (ASA) risk class of I to III;
- Body mass index (BMI) between 17 and 40 inclusive.
Who cannot join
- Has known allergies to opioids, or hypersensitivity to other materials (such as infusion line) or medications to be used in the study;
- Has a known or suspected history of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)-diagnosed alcohol, opiate or other drug abuse or dependence within 12 months prior to screening;
- Is unable to refrain from alcohol consumption for a period beginning 24 hours prior to surgery through the end of the Treatment Period;
- Is scheduled to undergo a hysterectomy that will utilize any type of robotic technology and/or a concomitant surgical procedure that would produce a significantly greater degree of surgical trauma than the laparoscopic hysterectomy or laparoscopic assisted vaginal hysterectomy alone;
- Has taken non-opioid analgesics (including cyclooxygenase-2 [COX-2] inhibitors) or nonsteroidal anti-inflammatory drugs (NSAIDs) within 12 hours of the Baseline assessments;
- Has taken any opioid analgesics or used systemic steroids within 4 days of surgery OR has previously used opiates chronically for a period of ≥3 months;
Show all 22Show fewer
- Has used antipsychotics, antiepileptics, sedatives, hypnotics, or antianxiety agents, selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants for < 30 days prior to surgery or had a dose change within the previous 30 days;
- Has taken any prescription or over-the-counter medication within 3 days prior to surgery that, in the opinion of the Investigator, is expected to confound the analgesic response;
- Has taken herbal agents or nutraceuticals (i.e., chaparral, comfrey, germander, gin bu huan, kava, pennyroyal, skullcap, St. John's wort, or valerian) 7 days prior to surgery;
- In the opinion of Investigator shows clinical signs of hypovolemia;
- Has an oxygen saturation < 92% on room air at Screening or prior to receiving the first infusion of study drug;
- Has any history of clinically significant cardiovascular disease,
- Has a clinically significant abnormal electrocardiogram (ECG) or a history of additional risk factors for torsades de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome);
- Has a history of any serious medical conditions that in the opinion of the Investigator would preclude study participation;
- Has serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, or gamma glutamyl transferase (GGT) >2.5 x the upper limit of normal (ULN) at screening;
- Has bilirubin, blood urea nitrogen (BUN), or creatinine >1.5 x the reference ULN at Screening;
- Has abnormally low hemoglobin < 10 mg/dl at Screening;
- Has serum sodium levels > 146 mmol/L at Screening;
- Has impaired renal function (creatinine clearance [CrCl] < 50 ml/min) at Screening;
- Has a positive test for human immunodeficiency virus (HIV) or known history of HIV infection;
- Has received another investigational drug within 30 days of scheduled surgery;
- Has a significant chronic pain condition in areas unrelated to the operative site at the time of Screening that in the Investigator's opinion could confound the interpretation of study results
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
United States18 sites
Visions Clinical Research
Boynton Beach, Florida, 33472
Cooper University Hospital
Camden, New Jersey, 08103
Chattanooga Medical Research
Chattanooga, Tennessee, 37404
Ohio State University Medical, Dept of Anesthesia
Columbus, Ohio, 43210
Woodland Healthcare California Clinical Research, Inc
Davis, California, 95616
Duke University
Durham, North Carolina, 27710
Riverside Clinical Research
Edgewater, Florida, 32132
Shoals Clinical Research Associates
Florence, Alabama, 35630
Texas Health Care, PLLC
Fort Worth, Texas, 76104
Palmetto Clinical Research,
Greenville, South Carolina, 29615
University of Miami, Dept of
Miami, Florida, 33136
Horizon Research Group
Mobile, Alabama, 36606
Wilmax
Mobile, Alabama, 36608
Drug Research and Analysis Corp
Montgomery, Alabama, 36106
Precision Clinical Trials
Phoenix, Arizona, 85032
Shoals Medical Trials, INC
Sheffield, Alabama, 35660
Olive View-UCLA Medical Center
Sylmar, California, 91342
Cypress Medical Research
Wichita, Kansas, 67226
About this study
Official title: A Multi-Center, Double-Randomized, Double Blind, Placebo Controlled Study to Evaluate the Analgesic Efficacy and Safety of Intravenous CR845 Dosed Preoperatively and Postoperatively in Patients Undergoing a Laparoscopic Hysterectomy
The primary purpose of this study is to determine if CR845 is effective in treating the pain associated with a laparoscopic hysterectomy.
Read the detailed description
Currently, the most widely used drugs to treat pain after surgery are opiates, such as morphine. Morphine works mainly by activating one of several types of opiate receptors that control some of our pain sensation - the so-called mu opiate receptors. These receptors are located in many areas of the brain and also outside of the brain. By activating these receptors, morphine provides significant pain relief, but also causes side effects that limit its use. Some of these side effects include: respiratory depression or arrest (slowed or stopped breathing), sedation (a state of calmness or extreme relaxation), euphoria (an exaggerated feeling of physical and mental well-being), constipation, nausea, vomiting, and drug addiction.
In order to avoid the side effects of morphine and other mu opiates, the present experimental drug CR845 was designed to work at a different type of opiate receptor - called kappa - that can also provide pain relief, by acting on sensory nerves outside the brain. CR845 was designed to penetrate the brain much less than other opiate drugs, which should result in pain relief similar to that of morphine, but with fewer side effects. Because CR845 activates kappa receptors instead of mu receptors, the side effects are different than with a morphine-type drug. In particular, kappa opiates, such as CR845, do not cause respiratory depression or arrest, euphoria, constipation, drug tolerance, physical drug dependence or drug addiction. For these reasons, CR845 may present a distinct advantage over other opiates that are currently used for pain relief and post-operative pain in particular.
- Conditions
- Postoperative Pain
- Being tested
- CR845, Placebo
- Keywords
- pain, acute pain, visceral pain, kappa agonist, opioid analgesics, peripheral nervous system agents, physiological effects of drugs, surgery, hysterectomy, post-operative, post-operative complications
- Medical subject headings
- Pain, Postoperative, Pain, Acute Pain, Visceral Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CR845Drug
Also called Preoperative Active Dose
Single i.v. dose (0.04 mg/kg) administered preoperatively
PlaceboDrug
Also called Preoperative Placebo Dose
Single i.v. dose administered preoperatively
CR845Drug
Also called Postoperative Active for Pain
Single i.v. dose (0.04 mg/kg) administered postoperatively for pain
PlaceboDrug
Also called Postoperative Placebo for Pain
Single i.v. dose administered postoperatively for pain
| Study group | Role | What they receive |
|---|---|---|
| CR845 | Experimental | Peripheral kappa opioid receptor agonist Receives: Drug: CR845 |
| Placebo | Placebo comparator | Matched Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Morphine Consumption in the First 24 Hours Following Postoperative Study Drug Treatment
Measured: 24 hours
Secondary outcomes (6)
Summed Pain Intensity Difference From 0-24 Hours (SPID 0-24) Following Postoperative Study Drug Treatment Using Last Observation Carried Forward (LOCF)
Patients reported their pain intensity using a visual analogue scale (VAS) from 0 to 100 mm, where 0 mm represented "No Pain" and 100 mm represented the "Worst Pain You Can Imagine". SPID 0-24 represents the cumulative time-weighted sum of the pain intensity difference (PID) scores between each assessment timepoint following the postoperative administration of study drug (i.e. 0 to 15 min, 15 to 30 min, etc.) over 24 hours. Pain intensity assessments were measured at baseline (entry pain score), then at 15, 30, 45, 60, 90, 120, 150, 180, 240, 360, 480, 720, 960, and 1440 minutes after the start of the infusion of study drug following surgery.
Negative SPID values represent a decrease in pain intensity (i.e. lower values indicate a greater reduction in pain).
Measured: 0 to 24 hours
Morphine Consumption Following Postoperative Study Drug Treatment in the 2-24 Hour Period After Recovery in the Post-Anesthesia Care Unit (Post-PACU)
Measured: 2 to 24 hours (post-PACU)
Total Pain Relief Within the First 2 Hours (TOTPAR 0-2) Following Postoperative Study Drug Treatment Using LOCF
Patients reported their pain relief using a 5-point categorical scale of 0 to 4 (0 = No Relief, 1 = A Little Relief, 2 = Some Relief, 3 = A Lot of Relief and 4 = Complete Relief). TOTPAR 0-2 was represents the cumulative time-weighted sum of the pain relief (PR) scores between each assessment timepoint following the postoperative administration of study drug (i.e. 15 to 30 min, 30 to 45 min, etc.) over the first 2 hours. Pain relief assessments were measured at 15, 30, 45, 60, 90, 120 minutes after the start of the infusion of study drug following surgery.
Positive TOTPAR values represent an increase in pain relief.
Measured: 0 to 2 hours
Global Evaluation Responder Analysis
Responders = Excellent or Very Good; Non-Responders = Fair or Poor. Patient who reported a score of "Good" were not included in the analysis as the midpoint cannot be unambiguously assigned for a binary outcome measurement.
Measured: At 24 hours
Total Number of Patients Reporting At Least One Episode of Nausea
Measured: Up to 24 hours
Total Number of Patients Reporting At Least One Episode of Vomiting
Measured: Up to 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2011 (estimated)
- Study startJul 2011
- Primary completionApr 2012
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Postoperative PainStudies 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 203 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cara Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tong-Joo Gan, MD, MHS, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01361568
- Sponsor's protocol ID
- CR845 CLIN2002
- Status last verified
- May 2014
- First submitted
- 25 May 2011
- Last updated
- 29 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center, Double-Randomized, Double Blind, Placebo Controlled Study to Evaluate the Analgesic Efficacy and Safety of Intravenous CR845 Dosed Preoperatively and Postoperatively in Patients Undergoing a Laparoscopic Hysterectomy
- ClinicalTrials.gov ID
- NCT01361568
- Acronym / sponsor ID
- CR845 CLIN2002
- Conditions
- Postoperative Pain
- Keywords
- pain, acute pain, visceral pain, kappa agonist, opioid analgesics, peripheral nervous system agents, physiological effects of drugs, surgery
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 203 participants (actual)
- Lead sponsor
- Cara Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- Jul 2011
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 27 May 2011 (estimated)
- Results
- Posted 19 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study is to determine if CR845 is effective in treating the pain associated with a laparoscopic hysterectomy.
Detailed description
Currently, the most widely used drugs to treat pain after surgery are opiates, such as morphine. Morphine works mainly by activating one of several types of opiate receptors that control some of our pain sensation - the so-called mu opiate receptors. These receptors are located in many areas of the brain and also outside of the brain. By activating these receptors, morphine provides significant pain relief, but also causes side effects that limit its use. Some of these side effects include: respiratory depression or arrest (slowed or stopped breathing), sedation (a state of calmness or extreme relaxation), euphoria (an exaggerated feeling of physical and mental well-being), constipation, nausea, vomiting, and drug addiction.
In order to avoid the side effects of morphine and other mu opiates, the present experimental drug CR845 was designed to work at a different type of opiate receptor - called kappa - that can also provide pain relief, by acting on sensory nerves outside the brain. CR845 was designed to penetrate the brain much less than other opiate drugs, which should result in pain relief similar to that of morphine, but with fewer side effects. Because CR845 activates kappa receptors instead of mu receptors, the side effects are different than with a morphine-type drug. In particular, kappa opiates, such as CR845, do not cause respiratory depression or arrest, euphoria, constipation, drug tolerance, physical drug dependence or drug addiction. For these reasons, CR845 may present a distinct advantage over other opiates that are currently used for pain relief and post-operative pain in particular.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CR845 | Experimental | Drug: CR845Peripheral kappa opioid receptor agonist |
| Placebo | Placebo comparator | Drug: PlaceboMatched Placebo |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Able to provide written informed consent prior to any study procedures;
- Able to communicate clearly with the Investigator and staff;
- Female between 21 and 65 years of age, inclusive;
- Scheduled for elective laparoscopic hysterectomy under general anesthesia;
- Negative result on serum pregnancy test at screening and negative urine pregnancy test at Baseline (for women of child-bearing potential only) and not currently breast feeding, or planning to do so within 30 days of dosing;
Key exclusion criteria (22 listed)
- Has known allergies to opioids, or hypersensitivity to other materials (such as infusion line) or medications to be used in the study;
- Has a known or suspected history of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)-diagnosed alcohol, opiate or other drug abuse or dependence within 12 months prior to screening;
- Is unable to refrain from alcohol consumption for a period beginning 24 hours prior to surgery through the end of the Treatment Period;
- Is scheduled to undergo a hysterectomy that will utilize any type of robotic technology and/or a concomitant surgical procedure that would produce a significantly greater degree of surgical trauma than the laparoscopic hysterectomy or laparoscopic assisted vaginal hysterectomy alone;
- Has taken non-opioid analgesics (including cyclooxygenase-2 [COX-2] inhibitors) or nonsteroidal anti-inflammatory drugs (NSAIDs) within 12 hours of the Baseline assessments;
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 |
|---|---|---|
| CR845Also: Preoperative Active DoseSingle i.v. dose (0.04 mg/kg) administered preoperatively | Drug | CR845 |
| PlaceboAlso: Preoperative Placebo DoseSingle i.v. dose administered preoperatively | Drug | Placebo |
| CR845Also: Postoperative Active for PainSingle i.v. dose (0.04 mg/kg) administered postoperatively for pain | Drug | CR845 |
| PlaceboAlso: Postoperative Placebo for PainSingle i.v. dose administered postoperatively for pain | Drug | Placebo |
Primary outcome
Total Morphine Consumption in the First 24 Hours Following Postoperative Study Drug Treatment
Time frame: 24 hours
6 secondary outcomes
Summed Pain Intensity Difference From 0-24 Hours (SPID 0-24) Following Postoperative Study Drug Treatment Using Last Observation Carried Forward (LOCF)
Time frame: 0 to 24 hours
Morphine Consumption Following Postoperative Study Drug Treatment in the 2-24 Hour Period After Recovery in the Post-Anesthesia Care Unit (Post-PACU)
Time frame: 2 to 24 hours (post-PACU)
Total Pain Relief Within the First 2 Hours (TOTPAR 0-2) Following Postoperative Study Drug Treatment Using LOCF
Time frame: 0 to 2 hours
Global Evaluation Responder Analysis
Time frame: At 24 hours
Total Number of Patients Reporting At Least One Episode of Nausea
Time frame: Up to 24 hours
Total Number of Patients Reporting At Least One Episode of Vomiting
Time frame: Up to 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Tong-Joo Gan, MD, MHS principal investigator
Duke University
18 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 in people with Postoperative Pain, run by Cara Therapeutics, Inc. at 18 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 8 inclusion and 22 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 29 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 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 19 May 2014). 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?
Total Morphine Consumption in the First 24 Hours Following Postoperative Study Drug Treatment (time frame: 24 hours). 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 29 May 2014; AzTrials last refreshed its copy on 7 Nov 2026.