Trial Outcomes & Findings for A Trial to Evaluate CG5503 Efficacy and Safety in Acute Pain After Bunionectomy (NCT NCT00609466)

Last Updated: 2011-11-16

Results Overview

Pain Intensity assessed at predefined time points over a 48 hour period using an 11-point Numeric Rating Scale (NRS) where a score of zero indicates "no pain" and a score of ten indicates "pain as bad as you can imagine". Differences calculated as \[baseline-post baseline\] at each predefined time point. The theoretical maximum range of Sum of pain intensity differences (SPID48) is from -480 (indicative of an increase in pain) to 480 (indicative of a decrease in pain).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

291 participants

Primary outcome timeframe

Baseline value to 48 hours after first study drug intake.

Results posted on

2011-11-16

Participant Flow

The recruitment period for this in-patient, multicenter study occurred between 04 September 2007 and 11 December 2007.

The trial consisted of a Screening Period (Day -28 up to the first surgical incision on Day -1), a Surgical Period (Day -1 to Day 1 at approximately 03:00 h.), a Qualification Period (Day 1), a Double-Blind Treatment Period (Day 1 up to Day 4), and a Follow-up Period (Day 8 up to Day 18).

Participant milestones

Participant milestones
Measure	CG5503 CG5503 IR 75mg 4-6 hourly	Morphine Morphine IR 30mg 4 to 6 hourly	Placebo Matching Placebo 4 to 6 hourly
Overall Study STARTED	96	96	99
Overall Study COMPLETED	94	90	95
Overall Study NOT COMPLETED	2	6	4

Reasons for withdrawal

Reasons for withdrawal
Measure	CG5503 CG5503 IR 75mg 4-6 hourly	Morphine Morphine IR 30mg 4 to 6 hourly	Placebo Matching Placebo 4 to 6 hourly
Overall Study Withdrawal by Subject	0	1	1
Overall Study Adverse Event	2	3	1
Overall Study Lack of Efficacy	0	2	2

Baseline Characteristics

A Trial to Evaluate CG5503 Efficacy and Safety in Acute Pain After Bunionectomy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CG5503 n=96 Participants CG5503 IR 75mg 4-6 hourly	Morphine n=96 Participants Morphine IR 30mg 4 to 6 hourly	Placebo n=99 Participants Matching Placebo 4 to 6 hourly	Total n=291 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	94 Participants n=5 Participants	88 Participants n=7 Participants	90 Participants n=5 Participants	272 Participants n=4 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	17 Participants n=4 Participants
Age Continuous	44.6 years STANDARD_DEVIATION 12.58 • n=5 Participants	43.7 years STANDARD_DEVIATION 14.19 • n=7 Participants	43.8 years STANDARD_DEVIATION 13.93 • n=5 Participants	44.0 years STANDARD_DEVIATION 13.55 • n=4 Participants
Sex: Female, Male Female	83 Participants n=5 Participants	73 Participants n=7 Participants	88 Participants n=5 Participants	244 Participants n=4 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	23 Participants n=7 Participants	11 Participants n=5 Participants	47 Participants n=4 Participants
Region of Enrollment United States	96 participants n=5 Participants	96 participants n=7 Participants	99 participants n=5 Participants	291 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline value to 48 hours after first study drug intake.

Population: Intention to Treat - randomized subjects who were dosed and had a baseline pain intensity assessment. Last observation carried forward was used.

Outcome measures

Outcome measures
Measure	CG5503 n=96 Participants CG5503 IR 75mg 4-6 hourly	Morphine n=93 Participants Morphine IR 30mg 4 to 6 hourly	Placebo n=96 Participants Matching Placebo 4 to 6 hourly
Sum of Pain Intensity Differences Relative to the Baseline Pain Intensity.	46.2 units Standard Deviation 130.83	102.5 units Standard Deviation 153.26	-17.5 units Standard Deviation 111.27

SECONDARY outcome

Timeframe: Baseline up to 72 hours after first study drug intake

Population: Intention to treat (ITT) and Last Observation Carried Forward (LOCF)

Number of participants who used at least one dose of rescue medication during the 72 hour double blind period.

Outcome measures

Outcome measures
Measure	CG5503 n=96 Participants CG5503 IR 75mg 4-6 hourly	Morphine n=93 Participants Morphine IR 30mg 4 to 6 hourly	Placebo n=96 Participants Matching Placebo 4 to 6 hourly
Number of Participants Using Rescue Medication	62 participants	46 participants	82 participants

SECONDARY outcome

Timeframe: Baseline to 48 hours after first study drug intake

Population: Intention to treat(ITT)and Last Observation Carried Forward (LOCF)

Total pain relief (TOTPAR) in the 48 hour period from the first dose of study drug. The subject was to indicate pain relief at rest in response to the following question: How much relief have you had from your starting pain? None = 0, A little = 1, Some = 2, A lot = 3 and Complete = 4. The theoretical maximum range of Total pain relief (TOTPAR)48 is from 0 (indicative of no pain relief) to 192. The higher the value the better the pain relief.

Outcome measures

Outcome measures
Measure	CG5503 n=96 Participants CG5503 IR 75mg 4-6 hourly	Morphine n=93 Participants Morphine IR 30mg 4 to 6 hourly	Placebo n=96 Participants Matching Placebo 4 to 6 hourly
Total Pain Relief (TOTPAR)	79.2 units Standard Deviation 49.63	81.6 units Standard Deviation 56.30	41.8 units Standard Deviation 50.88

SECONDARY outcome

Timeframe: Baseline to 6 hours after intake of first study drug

Population: Intention to treat(ITT) and Last Observation Carried Forward (LOCF).

Pain Intensity assessed at predefined time points over a 6 hour period using an 11-point Numeric Rating Scale (NRS) where a score of zero indicates "no pain" and a score of ten indicates "pain as bad as you can imagine". Differences calculated as \[baseline-post baseline\] at each predefined time point. The theoretical maximum range of Sum of pain intensity differences (SPID6) is from -60 (indicative of an increase in pain) to 60 (indicative of a decrease in pain).

Outcome measures

Outcome measures
Measure	CG5503 n=96 Participants CG5503 IR 75mg 4-6 hourly	Morphine n=93 Participants Morphine IR 30mg 4 to 6 hourly	Placebo n=96 Participants Matching Placebo 4 to 6 hourly
Sum of Pain Intensity Differences Over 6 Hours (SPID6) Relative to the Baseline Pain Intensity	8.0 units Standard Deviation 13.51	8.0 units Standard Deviation 15.59	-1.2 units Standard Deviation 13.10

SECONDARY outcome

Timeframe: Baseline to 12 hours after first study drug intake

Population: Intention to treat (ITT) and Last Observation Carried Forward (LOCF).

Pain Intensity assessed at predefined time points over a 12 hour period using an 11-point Numeric Rating Scale (NRS) where a score of zero indicates "no pain" and a score of ten indicates "pain as bad as you can imagine". Differences calculated as \[baseline-post baseline\] at each predefined time point. The theoretical maximum range of Sum of pain intensity differences (SPID12) is from -120 (indicative of an increase in pain) to 120 (indicative of a decrease in pain).

Outcome measures

Outcome measures
Measure	CG5503 n=96 Participants CG5503 IR 75mg 4-6 hourly	Morphine n=93 Participants Morphine IR 30mg 4 to 6 hourly	Placebo n=96 Participants Matching Placebo 4 to 6 hourly
Sum of Pain Intensity Differences Over 12 Hours (SPID12) Relative to the Baseline Pain Intensity	14.4 units Standard Deviation 28.89	17.9 units Standard Deviation 32.12	-4.7 units Standard Deviation 24.82

SECONDARY outcome

Timeframe: Baseline to 24 hours after first study drug intake

Population: Intention to treat (ITT)and Last Observation Carried Forward (LOCF).

Pain Intensity assessed at predefined time points over a 24 hour period using an 11-point Numeric Rating Scale (NRS) where a score of zero indicates "no pain" and a score of ten indicates "pain as bad as you can imagine". Differences calculated as \[baseline-post baseline\] at each predefined time point. The theoretical maximum range of Sum of pain intensity differences (SPID24) is from -240 (indicative of an increase in pain) to 240 (indicative of a decrease in pain).

Outcome measures

Outcome measures
Measure	CG5503 n=96 Participants CG5503 IR 75mg 4-6 hourly	Morphine n=93 Participants Morphine IR 30mg 4 to 6 hourly	Placebo n=96 Participants Matching Placebo 4 to 6 hourly
Sum of Pain Intensity Differences Over 24 Hours (SPID24) Relative to the Baseline Pain Intensity	22.3 units Standard Deviation 60.17	41.3 units Standard Deviation 68.96	-10.7 units Standard Deviation 51.28

SECONDARY outcome

Timeframe: Baseline to 72 hours after first intake of study drug

Population: Intention to treat (ITT) and Last Observation Carried Forward (LOCF).

Pain Intensity assessed at predefined time points over a 72 hour period using an 11-point Numeric Rating Scale (NRS) where a score of zero indicates "no pain" and a score of ten indicates "pain as bad as you can imagine". Differences calculated as \[baseline-post baseline\] at each predefined time point. The theoretical maximum range of Sum of pain intensity differences (SPID72) is from -720 (indicative of an increase in pain) to 720 (indicative of a decrease in pain).

Outcome measures

Outcome measures
Measure	CG5503 n=96 Participants CG5503 IR 75mg 4-6 hourly	Morphine n=93 Participants Morphine IR 30mg 4 to 6 hourly	Placebo n=96 Participants Matching Placebo 4 to 6 hourly
Sum of Pain Intensity Differences Over 72 Hours (SPID72) Relative to the Baseline Pain Intensity	78.4 units Standard Deviation 212.05	174.1 units Standard Deviation 242	-19.1 units Standard Deviation 179.48

Adverse Events

CG5503

Serious events: 0 serious events

Other events: 69 other events

Deaths: 0 deaths

Morphine

Serious events: 1 serious events

Other events: 85 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	CG5503 CG5503 IR 75mg 4-6 hourly	Morphine Morphine IR 30mg 4 to 6 hourly	Placebo Matching Placebo 4 to 6 hourly
Skin and subcutaneous tissue disorders Stevens Johnson Syndrome	0.00% 0/96	1.0% 1/96 • Number of events 1	0.00% 0/99

Other adverse events

Other adverse events
Measure	CG5503 CG5503 IR 75mg 4-6 hourly	Morphine Morphine IR 30mg 4 to 6 hourly	Placebo Matching Placebo 4 to 6 hourly
Gastrointestinal disorders Nausea	47.9% 46/96 • Number of events 79	67.7% 65/96 • Number of events 147	24.2% 24/99 • Number of events 34
Gastrointestinal disorders Vomiting	21.9% 21/96 • Number of events 40	58.3% 56/96 • Number of events 156	4.0% 4/99 • Number of events 8
Gastrointestinal disorders Constipation	11.5% 11/96 • Number of events 11	13.5% 13/96 • Number of events 13	5.1% 5/99 • Number of events 6
Gastrointestinal disorders Dry Mouth	6.2% 6/96 • Number of events 8	8.3% 8/96 • Number of events 8	0.00% 0/99
Nervous system disorders Dizziness	30.2% 29/96 • Number of events 62	24.0% 23/96 • Number of events 39	17.2% 17/99 • Number of events 25
Nervous system disorders Headache	19.8% 19/96 • Number of events 27	29.2% 28/96 • Number of events 38	24.2% 24/99 • Number of events 32
Nervous system disorders Somnolence	12.5% 12/96 • Number of events 17	13.5% 13/96 • Number of events 15	4.0% 4/99 • Number of events 4
Skin and subcutaneous tissue disorders Pruritus	15.6% 15/96 • Number of events 29	20.8% 20/96 • Number of events 25	0.00% 0/99
Skin and subcutaneous tissue disorders Pruritus generalised	4.2% 4/96 • Number of events 5	17.7% 17/96 • Number of events 21	2.0% 2/99 • Number of events 2
Skin and subcutaneous tissue disorders Erythema	1.0% 1/96 • Number of events 1	7.3% 7/96 • Number of events 7	2.0% 2/99 • Number of events 2
Investigations Alanine aminotransferase increased	1.0% 1/96 • Number of events 1	7.3% 7/96 • Number of events 7	2.0% 2/99 • Number of events 2
Investigations Aspartate aminotransferase increased	1.0% 1/96 • Number of events 1	5.2% 5/96 • Number of events 5	1.0% 1/99 • Number of events 1
Investigations Gamma glutamyl transferase increased	1.0% 1/96 • Number of events 1	7.3% 7/96 • Number of events 7	4.0% 4/99 • Number of events 4
Metabolism and nutrition disorders Decreased appetite	0.00% 0/96	6.2% 6/96 • Number of events 6	0.00% 0/99

Additional Information

René Allard

Grunenthal

Phone: 49 241 569 3223

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Grünenthal GmbH reserves the right to review any publication pertaining to the trial before it is submitted for publication. Neither Grünenthal nor the investigator has the right to prohibit publication unless publication can be shown to affect possible patent rights.
Publication restrictions are in place

Restriction type: OTHER