Trial Outcomes & Findings for A Phase 2 Study to Evaluate Analgesic Effect of IV CR845 For Pain Following Bunionectomy Surgery (NCT NCT01789476)

Last Updated: 2015-04-30

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

51 participants

Primary outcome timeframe

0 to 24 hours

Results posted on

2015-04-30

Participant Flow

Participant milestones

Participant milestones
Measure	CR845 CR845 (0.005 mg/kg) IV	Placebo Matched placebo
Overall Study STARTED	34	17
Overall Study COMPLETED	26	15
Overall Study NOT COMPLETED	8	2

Reasons for withdrawal

Reasons for withdrawal
Measure	CR845 CR845 (0.005 mg/kg) IV	Placebo Matched placebo
Overall Study Lack of Efficacy	6	2
Overall Study Adverse Event	1	0
Overall Study Unable to get IV access	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CR845 n=34 Participants CR845 (0.005 mg/kg) IV	Placebo n=17 Participants Matched placebo	Total n=51 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	32 Participants n=5 Participants	16 Participants n=7 Participants	48 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants	16 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=5 Participants	17 Participants n=7 Participants	46 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	32 Participants n=5 Participants	15 Participants n=7 Participants	47 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	34 participants n=5 Participants	17 participants n=7 Participants	51 participants n=5 Participants

PRIMARY outcome

Timeframe: 0 to 24 hours

Population: The analysis included all patients in the Completer population who completed the trial, where time 0 was the start time of the first dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=15 Participants Matched placebo	CR845 n=26 Participants CR845 (0.005 mg/kg) IV
Summed Pain Intensity Differences Over 24 Hours (SPID 0-24) Following the Initial Administration of Study Drug	-52.08 units on a scale * hours Standard Deviation 395.02	-292.7 units on a scale * hours Standard Deviation 390.52

SECONDARY outcome

Timeframe: Up to 36 hours

Population: The analysis included all patients in the Completer population who completed the trial, where time 0 was the start time of the first dose 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).

Outcome measures

Outcome measures
Measure	Placebo n=15 Participants Matched placebo	CR845 n=26 Participants CR845 (0.005 mg/kg) IV
Summed Pain Intensity Differences Over 36 Hours (SPID 0-36) Following the Initial Administration of Study Drug	-259.2 units on a scale * hours Standard Deviation 533.24	-675.6 units on a scale * hours Standard Deviation 658.0

SECONDARY outcome

Timeframe: Up to 48 hours

Population: The analysis included all patients in the Completer population who completed the trial, where time 0 was the start time of the first dose 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).

Outcome measures

Outcome measures
Measure	Placebo n=15 Participants Matched placebo	CR845 n=26 Participants CR845 (0.005 mg/kg) IV
Summed Pain Intensity Differences Over 48 Hours (SPID 0-48) Following the Initial Administration of Study Drug	-534.4 units on a scale * hours Standard Deviation 724.8	-1117 units on a scale * hours Standard Deviation 954.8

Adverse Events

CR845

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Frédérique Menzaghi, PhD, Vice President Research & Development

Cara Therapeutics, Inc.

Phone: (203) 567-1502

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	CR845 n=34 participants at risk CR845 (0.005 mg/kg) IV	Placebo n=17 participants at risk Matched placebo
Nervous system disorders Dizziness	29.4% 10/34 • Number of events 10 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	23.5% 4/17 • Number of events 4 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
Nervous system disorders Paraesthesia	29.4% 10/34 • Number of events 13 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	0.00% 0/17 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
Nervous system disorders Somnolence	20.6% 7/34 • Number of events 7 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	0.00% 0/17 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
Nervous system disorders Headache	8.8% 3/34 • Number of events 3 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	5.9% 1/17 • Number of events 1 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
Nervous system disorders Hypoaesthesia	8.8% 3/34 • Number of events 3 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	0.00% 0/17 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
Gastrointestinal disorders Nausea	23.5% 8/34 • Number of events 8 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	58.8% 10/17 • Number of events 13 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
Gastrointestinal disorders Constipation	8.8% 3/34 • Number of events 3 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	5.9% 1/17 • Number of events 1 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
Gastrointestinal disorders Dry mouth	5.9% 2/34 • Number of events 2 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	0.00% 0/17 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
Gastrointestinal disorders Vomiting	5.9% 2/34 • Number of events 2 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	29.4% 5/17 • Number of events 7 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
Gastrointestinal disorders Diarrhoea	2.9% 1/34 • Number of events 1 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	5.9% 1/17 • Number of events 1 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
General disorders Infusion site bruising	5.9% 2/34 • Number of events 2 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	5.9% 1/17 • Number of events 1 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
General disorders Feeling hot	2.9% 1/34 • Number of events 1 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	5.9% 1/17 • Number of events 1 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
General disorders Injection site discharge	2.9% 1/34 • Number of events 1 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	5.9% 1/17 • Number of events 1 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
General disorders Infusion site erythema	0.00% 0/34 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	11.8% 2/17 • Number of events 2 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
General disorders Oedema peripheral	0.00% 0/34 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	5.9% 1/17 • Number of events 1 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
General disorders Pain	0.00% 0/34 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	5.9% 1/17 • Number of events 1 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
Musculoskeletal and connective tissue disorders Neck pain	5.9% 2/34 • Number of events 2 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	0.00% 0/17 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/34 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	5.9% 1/17 • Number of events 1 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
Skin and subcutaneous tissue disorders Hyperhidrosis	5.9% 2/34 • Number of events 2 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	5.9% 1/17 • Number of events 1 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
Investigations Aspartate aminotransferase increased	5.9% 2/34 • Number of events 2 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	5.9% 1/17 • Number of events 1 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
Investigations Alanine aminotransferase increased	2.9% 1/34 • Number of events 1 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	5.9% 1/17 • Number of events 1 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
Metabolism and nutrition disorders Decreased appetite	2.9% 1/34 • Number of events 1 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	5.9% 1/17 • Number of events 1 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
Infections and infestations Urinary tract infection	0.00% 0/34 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	5.9% 1/17 • Number of events 1 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/34 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).	5.9% 1/17 • Number of events 1 • Adverse events were recorded from the start of study drug administration to the Follow-up visit (up to Day 10 after surgery).