A Phase 2 interventional study of CR845 and Placebo in Acute Pain, sponsored by Cara Therapeutics, Inc.. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2015-04-30.
Sponsored by Cara Therapeutics, Inc. · Phase 2, Interventional, and Treatment
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.
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.
876 studies on the registry are indexed under Acute Pain; 154 are open to participants now.
This study's enrollment of 51 is below the median of 90 across 732 interventional studies indexed under Acute Pain.
Browse Acute Pain studies →Cara Therapeutics, Inc. is the lead sponsor of 24 studies on the registry; none are open to participants now.
Of its 15 completed or terminated interventional studies of FDA-regulated products, 5 (33%) have results posted.
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Exclusion Criteria:
Peripheral kappa opioid receptor agonist
Drug: CR845
Matched placebo
Drug: Placebo
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
Matching placebo administered using same dosing algorithm as the active arm
Also known as: Post-operative placebo for pain
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).
Time frame: 0 to 24 hours
Summed Pain Intensity Differences Over 36 Hours (SPID 0-36) 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 36 hours used in calculating SPID 0-36). Negative SPID values represent a decrease in pain intensity (i.e. lower values indicate a greater reduction in pain).
Time frame: Up to 36 hours
Summed Pain Intensity Differences Over 48 Hours (SPID 0-48) 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. Negative SPID values represent a decrease in pain intensity (i.e. lower values indicate a greater reduction in pain).
Time frame: Up to 48 hours
| Milestone | CR845 | Placebo |
|---|---|---|
| Started | 34 | 17 |
| Completed | 26 | 15 |
| Not completed | 8 | 2 |
| Withdrew: Lack of efficacy | 6 | 2 |
| Withdrew: Adverse event | 1 | 0 |
| Withdrew: Unable to get iv access | 1 | 0 |
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).
| units on a scale * hours | Placebo | CR845 |
|---|---|---|
| Summed Pain Intensity Differences Over 24 Hours (SPID 0-24) Following the Initial Administration of Study Drug | -52.08 ± 395.02 | -292.7 ± 390.52 |
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 36 hours used in calculating SPID 0-36). Negative SPID values represent a decrease in pain intensity (i.e. lower values indicate a greater reduction in pain).
| units on a scale * hours | Placebo | CR845 |
|---|---|---|
| Summed Pain Intensity Differences Over 36 Hours (SPID 0-36) Following the Initial Administration of Study Drug | -259.2 ± 533.24 | -675.6 ± 658.0 |
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. Negative SPID values represent a decrease in pain intensity (i.e. lower values indicate a greater reduction in pain).
| units on a scale * hours | Placebo | CR845 |
|---|---|---|
| Summed Pain Intensity Differences Over 48 Hours (SPID 0-48) Following the Initial Administration of Study Drug | -534.4 ± 724.8 | -1117 ± 954.8 |
Collected over Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| CR845 | — | 0/34 (0%) | 29/34 (85.3%) |
| Placebo | — | 0/17 (0%) | 14/17 (82.4%) |
| Event | CR845 | Placebo |
|---|---|---|
| NauseaGastrointestinal disorders | 8/34 | 10/17 |
| DizzinessNervous system disorders | 10/34 | 4/17 |
| ParaesthesiaNervous system disorders | 10/34 | 0/17 |
| VomitingGastrointestinal disorders | 2/34 | 5/17 |
| SomnolenceNervous system disorders | 7/34 | 0/17 |
| Infusion site erythemaGeneral disorders | 0/34 | 2/17 |
| HeadacheNervous system disorders | 3/34 | 1/17 |
| HypoaesthesiaNervous system disorders | 3/34 | 0/17 |
| ConstipationGastrointestinal disorders | 3/34 | 1/17 |
| Dry mouthGastrointestinal disorders | 2/34 | 0/17 |
Safety population
| Age, Categorical(Participants) | CR845 | Placebo | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 32 | 16 | 48 |
| >=65 years | 2 | 1 | 3 |
| Sex: Female, Male(Participants) | CR845 | Placebo | Total |
|---|---|---|---|
| Female | 29 | 16 | 45 |
| Male | 5 | 1 | 6 |
| Ethnicity (NIH/OMB)(Participants) | CR845 | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 5 | 0 | 5 |
| Not Hispanic or Latino | 29 | 17 | 46 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | CR845 | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 1 | 1 |
| Native Hawaiian or Other Pacific Islander | 1 | 0 | 1 |
| Black or African American | 1 | 1 | 2 |
| White | 32 | 15 | 47 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | CR845 | Placebo | Total |
|---|---|---|---|
| United States | 34 | 17 | 51 |
This study is completed, as verified in Apr 2015. You cannot join it, but the record below documents what was studied.
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Cara Therapeutics, Inc.