Study to Evaluate Analgesic Effect of Intravenous Administration of Kappa Agonist CR845 After Hysterectomy Surgery

Acute Pain Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00877799
• Other study ID #: CR845-CLIN2001
• Status: Completed
• Phase: Phase 2
• First received: April 6, 2009
• Last updated: April 23, 2015
• Start date: March 2009
• Est. completion date: January 2010

Study information

• Verified date: April 2015
• Source: Cara Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical 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. 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 114
• Est. completion date: January 2010
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 21 Years to 60 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Pain

Intervention

Drug:
• CR845
CR845 (0.024 mg/kg) administered the day after surgery (Day 1)
• CR845
CR845 (0.008 mg/kg) administered the day after surgery (Day 1)
• CR845
CR845 (0.040 mg/kg) administered immediately after surgery (Day 0)
• Placebo
Matched placebo administered the day after surgery (Day 1)
• Placebo
Matched placebo administered immediately after surgery (Day 0)

Locations

Country	Name	City	State
United States	The Ohio State University Medical Center	Columbus	Ohio
United States	Adventist Medical Center	Glendale	California
United States	Memorial Hermann - Memorial City Medical Center	Houston	Texas
United States	The Woman's Hospital of Texas	Houston	Texas
United States	Saddleback Memorial Hospital	Laguna Hills	California
United States	Palms West Hospital	Loxahatchee	Florida
United States	University of Miami/Jackson Memorial Hospital	Miami	Florida
United States	Mobile Infirmary Medical Center	Mobile	Alabama
United States	Springhill Medical Center	Mobile	Alabama
United States	Huntington Memorial Hospital	Pasadena	California
United States	Paradise Valley Hospital	Phoenix	Arizona
United States	Helen Keller Hospital	Sheffield	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
Cara Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Total PCA Morphine Consumption in the 4-8 Hour Period Following Postoperative Study Drug Treatment		4 to 8 hours	No
Other	Total PCA Morphine Consumption in the 8-16 Hour Period Following Postoperative Study Drug Treatment		8 to 16 hours	No
Primary	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.	15 and 30 minutes after study drug administration	No
Secondary	Total PCA Morphine Consumption in the 0-16 Hour Period Following Postoperative Study Drug Treatment		0 to 16 hours	No