Acute PainPhase 2NCT00877799
Study to Evaluate Analgesic Effect of Intravenous Administration of Kappa Agonist CR845 After Hysterectomy Surgery
A Phase 2 study testing CR845 in people with Acute Pain, run by Cara Therapeutics, Inc. at 12 sites in United States.
Trial summary
The purpose of this study is to determine the effectiveness and safety of single intravenous doses of the kappa opioid agonist CR845 in relieving pain in patients following laparoscopic-assisted hysterectomy surgery. Read more about this study
- Who is it for?
- Ages 21 to 60 years, women only
- Conditions the study is for
- Acute 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
- 114 participants
- Where
- 12 sitesUnited States
- Study dates
- Mar 2009to Jan 2010
- 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 60 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- The patients will have an elective laparoscopic-assisted hysterectomy under general anesthesia.
- The patient's preoperative health is graded as the American Society of Anesthesiologists (ASA) risk class of I to III
Who cannot join
- The patient has a history of known allergies to opioids
- The patient is currently taking opioid analgesics chronically or took opioid analgesics on at least 4 days during the week before surgery.
- Patients having additional procedures (such as those involving the bladder) at the same time as the laparoscopic-assisted hysterectomy.
- Patients taking short-acting oral analgesics (eg, acetaminophen, aspirin, ibuprofen, ketorolac) within 6 hours before administration of study drug; long-acting nonsteroidal anti-inflammatory drugs (NSAIDs) (eg, naproxen, oxaprozin, piroxicam, celecoxib) within 3 days before administration of study drug; systemic steroids within 72 hours before administration of study drug; or any opioid analgesics or tramadol daily for greater than 10 days of the last 30 days before administration of study drug.
- Patients taking the following herbal agents or nutraceuticals within 7 days prior to beginning of the study: chaparral, comfrey, germander, gin bu huan, kava, pennyroyal, skullcap, St. John's wort, or valerian.
- Patients with clinically significant cardiovascular disease, or cardiac arrhythmias, or significant major risk factors for cardiovascular disease such as poorly controlled hypertension, poorly controlled hypercholesterolemia, poorly controlled diabetes mellitus or serious medical conditions, such as cancer.
- Patient has a history of hepatitis B or C or HIV infection with positive hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus (HCV) antibody test.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
The Ohio State University Medical Center
Columbus, Ohio, 43210
Adventist Medical Center
Glendale, California, 91206
Memorial Hermann - Memorial City Medical Center
Houston, Texas, 77024
The Woman's Hospital of Texas
Houston, Texas, 77054
Saddleback Memorial Hospital
Laguna Hills, California, 92653
Palms West Hospital
Loxahatchee Groves, Florida, 33472
University of Miami/Jackson Memorial Hospital
Miami, Florida, 33136
Mobile Infirmary Medical Center
Mobile, Alabama, 36607
Springhill Medical Center
Mobile, Alabama, 36608
Huntington Memorial Hospital
Pasadena, California, 91105
Paradise Valley Hospital
Phoenix, Arizona, 85032
Helen Keller Hospital
Sheffield, Alabama, 35660
About this study
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Proof of Concept Study to Evaluate the Analgesic Efficacy and Safety of Intravenous CR845 During the Post-Operative Period in Subjects Undergoing Laparoscopic-Assisted Hysterectomy
The purpose of this study is to determine the effectiveness and safety of single intravenous doses of the kappa opioid agonist CR845 in relieving pain in patients following laparoscopic-assisted hysterectomy surgery. The study protocol was divided into two parts with subjects either dosed with study drug the day following surgery (Cohort 1), or immediately after surgery (Cohort 2).
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
- Acute 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
- Acute Pain, 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 Cohort 1: CR845 0.024 mg/kg
CR845 (0.024 mg/kg) administered the day after surgery (Day 1)
CR845Drug
Also called Cohort 1: CR845 0.008 mg/kg
CR845 (0.008 mg/kg) administered the day after surgery (Day 1)
CR845Drug
Also called Cohort 2: CR845 0.040 mg/kg
CR845 (0.040 mg/kg) administered immediately after surgery (Day 0)
PlaceboDrug
Also called Cohort 1: Matched placebo
Matched placebo administered the day after surgery (Day 1)
PlaceboDrug
Also called Cohort 2: Matched placebo
Matched placebo administered immediately after surgery (Day 0)
| Study group | Role | What they receive |
|---|---|---|
| CR845 | Experimental | CR845 administered as a single 15-min i.v. infusion at doses of 0.008 or 0.024 mg/kg on the day after surgery (Cohort 1), or at a dose of 0.040 mg/kg immediately after surgery (Cohort 2) Receives: Drug: CR845 |
| Placebo | Placebo comparator | Matched placebo administered as a single 15-min i.v. infusion on the day after surgery (Cohort 1), or the immediately after surgery (Cohort 2) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Responders on Pain Intensity(PI) and Pain Relief (PR) Composite Endpoint
The primary efficacy endpoint was the percentage of treatment responders compared to placebo. A responder was defined as a subject who had at least a 40% reduction in their pain intensity score and a pain relief score of "some," "a lot," or "complete" at 15 and 30 min following the start of the study drug infusion.
Measured: 15 and 30 minutes after study drug administration
Secondary outcomes (1)
Total PCA Morphine Consumption in the 0-16 Hour Period Following Postoperative Study Drug Treatment
Measured: 0 to 16 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2009 (estimated)
- Study startMar 2009
- Primary completionDec 2009
- Study completionJan 2010
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 Acute 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cara Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Frédérique Menzaghi, Ph.D., Study director, Cara Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00877799
- Sponsor's protocol ID
- CR845-CLIN2001
- Status last verified
- Apr 2015
- First submitted
- 6 Apr 2009
- Last updated
- 12 May 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Proof of Concept Study to Evaluate the Analgesic Efficacy and Safety of Intravenous CR845 During the Post-Operative Period in Subjects Undergoing Laparoscopic-Assisted Hysterectomy
- ClinicalTrials.gov ID
- NCT00877799
- Acronym / sponsor ID
- CR845-CLIN2001
- Conditions
- Acute 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
- 114 participants (actual)
- Lead sponsor
- Cara Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- Mar 2009
- Primary completion
- Dec 2009 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 8 Apr 2009 (estimated)
- Results
- Posted 12 May 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the effectiveness and safety of single intravenous doses of the kappa opioid agonist CR845 in relieving pain in patients following laparoscopic-assisted hysterectomy surgery. The study protocol was divided into two parts with subjects either dosed with study drug the day following surgery (Cohort 1), or immediately after surgery (Cohort 2).
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
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CR845 | Experimental | Drug: CR845CR845 administered as a single 15-min i.v. infusion at doses of 0.008 or 0.024 mg/kg on the day after surgery (Cohort 1), or at a dose of 0.040 mg/kg immediately after surgery (Cohort 2) |
| Placebo | Placebo comparator | Drug: PlaceboMatched placebo administered as a single 15-min i.v. infusion on the day after surgery (Cohort 1), or the immediately after surgery (Cohort 2) |
Who may qualify
- Ages
- 21 to 60 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- The patients will have an elective laparoscopic-assisted hysterectomy under general anesthesia.
- The patient's preoperative health is graded as the American Society of Anesthesiologists (ASA) risk class of I to III
Key exclusion criteria (7 listed)
- The patient has a history of known allergies to opioids
- The patient is currently taking opioid analgesics chronically or took opioid analgesics on at least 4 days during the week before surgery.
- Patients having additional procedures (such as those involving the bladder) at the same time as the laparoscopic-assisted hysterectomy.
- Patients taking short-acting oral analgesics (eg, acetaminophen, aspirin, ibuprofen, ketorolac) within 6 hours before administration of study drug; long-acting nonsteroidal anti-inflammatory drugs (NSAIDs) (eg, naproxen, oxaprozin, piroxicam, celecoxib) within 3 days before administration of study drug; systemic steroids within 72 hours before administration of study drug; or any opioid analgesics or tramadol daily for greater than 10 days of the last 30 days before administration of study drug.
- Patients taking the following herbal agents or nutraceuticals within 7 days prior to beginning of the study: chaparral, comfrey, germander, gin bu huan, kava, pennyroyal, skullcap, St. John's wort, or valerian.
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: Cohort 1: CR845 0.024 mg/kgCR845 (0.024 mg/kg) administered the day after surgery (Day 1) | Drug | CR845 |
| CR845Also: Cohort 1: CR845 0.008 mg/kgCR845 (0.008 mg/kg) administered the day after surgery (Day 1) | Drug | CR845 |
| CR845Also: Cohort 2: CR845 0.040 mg/kgCR845 (0.040 mg/kg) administered immediately after surgery (Day 0) | Drug | CR845 |
| PlaceboAlso: Cohort 1: Matched placeboMatched placebo administered the day after surgery (Day 1) | Drug | Placebo |
| PlaceboAlso: Cohort 2: Matched placeboMatched placebo administered immediately after surgery (Day 0) | Drug | Placebo |
Primary outcome
Responders on Pain Intensity(PI) and Pain Relief (PR) Composite Endpoint
Time frame: 15 and 30 minutes after study drug administration
The primary efficacy endpoint was the percentage of treatment responders compared to placebo. A responder was defined as a subject who had at least a 40% reduction in their pain intensity score and a pain relief score of "some," "a lot," or "complete" at 15 and 30 min following the start of the study drug infusion.
1 secondary outcome
Total PCA Morphine Consumption in the 0-16 Hour Period Following Postoperative Study Drug Treatment
Time frame: 0 to 16 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2015.
- 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.
Frédérique Menzaghi, Ph.D. study director
Cara Therapeutics, Inc.
12 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 Acute Pain, run by Cara Therapeutics, Inc. at 12 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 2 inclusion and 7 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 12 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 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 12 May 2015). 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?
Responders on Pain Intensity(PI) and Pain Relief (PR) Composite Endpoint (time frame: 15 and 30 minutes after study drug administration). 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 12 May 2015.