A Phase 2 Study to Evaluate Analgesic Effect of IV CR845 For Pain Following Bunionectomy Surgery

NCT01789476 | Completed Phase 2 Results

• 1 other identifier: CR845 CLIN2003
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, randomized, double blind, placebo controlled, parallel group proof of concept study to evaluate the analgesic efficacy as well as the safety, tolerability and pharmacokinetic profile of CR845 in patients with pain following bunionectomy surgery.

Conditions

Acute Pain

Keywords

pain; acute pain; kappa agonis; opioid analgesia; bunionectomy; peripheral nervous system agents; physiological effects of drugs; surgery; post-operative; post-operative complications

Outcome Measures

Primary Outcomes (1)

• Summed Pain Intensity Differences Over 24 Hours (SPID 0-24) Following the Initial Administration of Study Drug

  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) and at 15, 30, 45, 60, 90, 120 and 150 minutes; 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 hours after the first administration of study drug (only timepoints up to 24 hours used in calculating SPID 0-24). Negative SPID values represent a decrease in pain intensity (i.e. lower values indicate a greater reduction in pain).

  0 to 24 hours

Secondary Outcomes (2)

• Summed Pain Intensity Differences Over 36 Hours (SPID 0-36) Following the Initial Administration of Study Drug

  Up to 36 hours

• Summed Pain Intensity Differences Over 48 Hours (SPID 0-48) Following the Initial Administration of Study Drug

  Up to 48 hours

Study Arms (2)

CR845

EXPERIMENTAL

Peripheral kappa opioid receptor agonist

Drug: CR845

Placebo

PLACEBO COMPARATOR

Matched placebo

Drug: Placebo

Interventions

CR845 DRUG

CR845 dosage = 0.005 mg/kg per dose, IV bolus. The initial dose was administered upon reaching a qualifying pain intensity score and followed by a supplemental dose, if requested by patient for pain. Additional doses could be administered every 8 hours up to 48 hours.

Also known as: Active treatment for post-operative pain

CR845

Placebo DRUG

Matching placebo administered using same dosing algorithm as the active arm

Also known as: Post-operative placebo for pain

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide written informed consent prior to any study procedures;
• Able to communicate clearly with the Investigator and staff;
• Males and females aged 18 years or older;
• Scheduled for elective primary unilateral first metatarsal bunionectomy surgery (osteotomy and internal fixation) with no collateral procedures;
• Females physically incapable of childbearing potential (postmenopausal for more than 1 year or surgically sterile) or practicing an acceptable method of contraception (hormonal, barrier with spermicide, intrauterine device, vasectomized partner, or abstinence). Subjects using hormonal birth control must have received at least 1 cycle of treatment prior to randomization. All females of childbearing potential must have a negative pregnancy test and not be breast feeding at Baseline;
• Negative urine drug screen for drugs of abuse at Screening and at Baseline; a positive drug screen result may be permitted if the patient has been on a stable dose of an allowed medication for \>30 days (antipsychotics, antiepileptics, sedatives, hypnotics, or antianxiety agents, selective serotonin reuptake inhibitors \[SSRIs\], tricyclic antidepressants) or \>3 months (opioid analgesics or systemic steroids);
• American Society of Anesthesiologists (ASA) risk class of I to II;
• Body weight \<170 kg

You may not qualify if:

• Has known allergies to opioids, unless has subsequently tolerated other opioids and in the opinion of the PI could tolerate study drug;
• 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;
• 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 been using opiates chronically for a period of \< 3 months; (Note: Patients on stable chronic opioids for ≥ 3 months will need to discontinue them for 4 days prior to surgery);
• 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 4 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, jin bu huan, kava, pennyroyal, skullcap, St. John's wort, or valerian) during any of the 7 days prior to surgery;
• Has any clinically significant condition or a significant laboratory abnormality that would, in the Investigator's or designee's opinion, preclude study participation
• Has received another investigational drug within 30 days of scheduled surgery.

Sponsors & Collaborators

• Cara Therapeutics, Inc.: lead

Study Sites (1)

Jean Brown Research

Salt Lake City, Utah, 84124, United States

Location

MeSH Terms

Conditions

Acute Pain; Pain

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Frédérique Menzaghi, PhD, Vice President Research & Development
• Organization: Cara Therapeutics, Inc.

fmenzaghi@caratherapeutics.com

(203) 567-1502

Study Officials

• Derek Muse, MD

  Jean Brown Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2013
• First Posted: February 12, 2013
• Study Start: May 1, 2013
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: April 30, 2015
• Results First Posted: April 30, 2015

Record last verified: 2015-04

Locations

US (1)