Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Tapentadol (CG5503) in the Treatment of Acute Pain After Abdominal Hysterectomy (NCT NCT00478023)

Last Updated: 2019-10-28

Results Overview

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, assuming patients start with a baseline value of 10 and all subsequent values will be 0).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

854 participants

Primary outcome timeframe

Baseline to 24 hours after first intake of study drug

Results posted on

2019-10-28

Participant Flow

The recruitment period for this in-patient, multicenter study occurred between 19 May 2007 and 11 Mar 2008.

This trial consisted of 5 periods: a Screening (Day -28 to Day -4 to the Pre-operative Visit) a Surgical (Day -1 to 1), a Postoperative Qualification, a Double-blind Treatment(Day 1-4) and a Follow-up Period (4-14 days after the double-blind treatment). The results refer to randomized subjects.

Participant milestones

Participant milestones
Measure	Morphine Morphine IR 20mg 4-6 hourly	CG5503 50mg CG5503 IR 50mg 4 to 6 hourly	CG5503 75mg CG5503 IR 75mg 4 to 6 hourly	CG5503 100mg CG5503 IR 100mg 4 to 6 hourly	Placebo Matched Placebo 4 to 6 hourly
Overall Study STARTED	170	168	171	176	169
Overall Study COMPLETED	135	144	151	146	114
Overall Study NOT COMPLETED	35	24	20	30	55

Reasons for withdrawal

Reasons for withdrawal
Measure	Morphine Morphine IR 20mg 4-6 hourly	CG5503 50mg CG5503 IR 50mg 4 to 6 hourly	CG5503 75mg CG5503 IR 75mg 4 to 6 hourly	CG5503 100mg CG5503 IR 100mg 4 to 6 hourly	Placebo Matched Placebo 4 to 6 hourly
Overall Study Adverse Event	11	7	8	14	6
Overall Study Death	1	0	0	0	0
Overall Study Lack of Efficacy	11	10	4	5	41
Overall Study Lost to Follow-up	3	1	1	1	0
Overall Study Withdrawal by Subject	2	3	2	4	5
Overall Study Lack of pain, Technical difficulties	7	3	5	6	3

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Tapentadol (CG5503) in the Treatment of Acute Pain After Abdominal Hysterectomy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Morphine n=170 Participants Morphine IR 20mg 4-6 hourly	CG5503 50mg n=168 Participants CG5503 IR 50mg 4 to 6 hourly	CG5503 75mg n=171 Participants CG5503 IR 75mg 4 to 6 hourly	CG5503 100mg n=176 Participants CG5503 IR 100mg 4 to 6 hourly	Placebo n=169 Participants Matched Placebo 4 to 6 hourly	Total n=854 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	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Age, Categorical Between 18 and 65 years	165 Participants n=5 Participants	166 Participants n=7 Participants	170 Participants n=5 Participants	173 Participants n=4 Participants	166 Participants n=21 Participants	840 Participants n=8 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	14 Participants n=8 Participants
Age, Continuous	48.5 years STANDARD_DEVIATION 6.75 • n=5 Participants	47.0 years STANDARD_DEVIATION 5.56 • n=7 Participants	47.1 years STANDARD_DEVIATION 5.37 • n=5 Participants	47.5 years STANDARD_DEVIATION 6.43 • n=4 Participants	47.2 years STANDARD_DEVIATION 5.83 • n=21 Participants	47.5 years STANDARD_DEVIATION 6.03 • n=8 Participants
Sex/Gender, Customized Female	170 participants n=5 Participants	168 participants n=7 Participants	171 participants n=5 Participants	176 participants n=4 Participants	169 participants n=21 Participants	854 participants n=8 Participants
Region of Enrollment Serbia	15 participants n=5 Participants	15 participants n=7 Participants	16 participants n=5 Participants	16 participants n=4 Participants	15 participants n=21 Participants	77 participants n=8 Participants
Region of Enrollment Hungary	5 participants n=5 Participants	6 participants n=7 Participants	5 participants n=5 Participants	5 participants n=4 Participants	4 participants n=21 Participants	25 participants n=8 Participants
Region of Enrollment Slovakia	25 participants n=5 Participants	25 participants n=7 Participants	25 participants n=5 Participants	25 participants n=4 Participants	24 participants n=21 Participants	124 participants n=8 Participants
Region of Enrollment Poland	36 participants n=5 Participants	36 participants n=7 Participants	34 participants n=5 Participants	37 participants n=4 Participants	36 participants n=21 Participants	179 participants n=8 Participants
Region of Enrollment Ukraine	14 participants n=5 Participants	11 participants n=7 Participants	14 participants n=5 Participants	14 participants n=4 Participants	13 participants n=21 Participants	66 participants n=8 Participants
Region of Enrollment Romania	34 participants n=5 Participants	33 participants n=7 Participants	34 participants n=5 Participants	36 participants n=4 Participants	35 participants n=21 Participants	172 participants n=8 Participants
Region of Enrollment Russian Federation	21 participants n=5 Participants	21 participants n=7 Participants	21 participants n=5 Participants	22 participants n=4 Participants	22 participants n=21 Participants	107 participants n=8 Participants
Region of Enrollment Latvia	20 participants n=5 Participants	21 participants n=7 Participants	22 participants n=5 Participants	21 participants n=4 Participants	20 participants n=21 Participants	104 participants n=8 Participants

PRIMARY outcome

Timeframe: Baseline to 24 hours after first intake of study drug

Population: Intention to Treat (ITT) and Last Observation Carried Forward (LOCF), i.e. all randomized subjects who received any amount of Investigational Medicinal Product (IMP = study drug) and had a non missing baseline pain assessment.

Outcome measures

Outcome measures
Measure	Morphine n=164 Participants Morphine IR 20mg 4-6 hourly	CG5503 50mg n=163 Participants CG5503 IR 50mg 4 to 6 hourly	CG5503 75mg n=167 Participants CG5503 IR 75mg 4 to 6 hourly	CG5503 100mg n=172 Participants CG5503 IR 100mg 4 to 6 hourly	Placebo n=166 Participants Matched Placebo 4 to 6 hourly
Sum of Pain Intensity Differences Relative to the Baseline Pain Intensity.	48.8 units on scale Standard Deviation 41.0	49.0 units on scale Standard Deviation 39.87	52.4 units on scale Standard Deviation 41.85	52.9 units on scale Standard Deviation 40.95	29.0 units on scale Standard Deviation 44.98

SECONDARY outcome

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

Population: Intention to treat (ITT) and Last Observation Carried Forward (LOCF), i.e. all randomized subjects who received any amount of Investigational Medicinal Product (IMP = study drug) and had a non missing baseline pain assessment.

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, assuming patients start with a baseline value of 10 and all subsequent values will be 0).

Outcome measures

Outcome measures
Measure	Morphine n=164 Participants Morphine IR 20mg 4-6 hourly	CG5503 50mg n=163 Participants CG5503 IR 50mg 4 to 6 hourly	CG5503 75mg n=167 Participants CG5503 IR 75mg 4 to 6 hourly	CG5503 100mg n=172 Participants CG5503 IR 100mg 4 to 6 hourly	Placebo n=166 Participants Matched Placebo 4 to 6 hourly
Sum of Pain Intensity Differences Relative to the Baseline Pain Intensity	116.6 units on scale Standard Deviation 87.10	112.4 units on scale Standard Deviation 87.32	120.6 units on scale Standard Deviation 87.35	123.5 units on scale Standard Deviation 83.50	71.1 units on scale Standard Deviation 101.17

Adverse Events

Morphine

Serious events: 3 serious events

Other events: 99 other events

Deaths: 0 deaths

CG5503 50mg

Serious events: 0 serious events

Other events: 84 other events

Deaths: 0 deaths

CG5503 75mg

Serious events: 0 serious events

Other events: 96 other events

Deaths: 0 deaths

CG5503 100mg

Serious events: 1 serious events

Other events: 106 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 88 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Morphine n=170 participants at risk Morphine IR 20mg 4-6 hourly	CG5503 50mg n=168 participants at risk CG5503 IR 50mg 4 to 6 hourly	CG5503 75mg n=171 participants at risk CG5503 IR 75mg 4 to 6 hourly	CG5503 100mg n=176 participants at risk CG5503 IR 100mg 4 to 6 hourly	Placebo n=169 participants at risk Matched Placebo 4 to 6 hourly
Infections and infestations Bronchopneumonia	0.59% 1/170 • Number of events 1 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	0.00% 0/168 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	0.00% 0/171 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	0.00% 0/176 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	0.00% 0/169 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.59% 1/170 • Number of events 1 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	0.00% 0/168 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	0.00% 0/171 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	0.00% 0/176 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	0.00% 0/169 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.59% 1/170 • Number of events 1 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	0.00% 0/168 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	0.00% 0/171 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	0.00% 0/176 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	0.00% 0/169 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.
Cardiac disorders Sinus tachycardia	0.00% 0/170 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	0.00% 0/168 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	0.00% 0/171 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	0.57% 1/176 • Number of events 1 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	0.00% 0/169 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.
Psychiatric disorders Confusional state	0.00% 0/170 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	0.00% 0/168 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	0.00% 0/171 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	0.57% 1/176 • Number of events 1 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	0.00% 0/169 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.

Other adverse events

Other adverse events
Measure	Morphine n=170 participants at risk Morphine IR 20mg 4-6 hourly	CG5503 50mg n=168 participants at risk CG5503 IR 50mg 4 to 6 hourly	CG5503 75mg n=171 participants at risk CG5503 IR 75mg 4 to 6 hourly	CG5503 100mg n=176 participants at risk CG5503 IR 100mg 4 to 6 hourly	Placebo n=169 participants at risk Matched Placebo 4 to 6 hourly
Gastrointestinal disorders Nausea	18.2% 31/170 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	13.7% 23/168 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	19.3% 33/171 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	17.6% 31/176 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	12.4% 21/169 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.
Gastrointestinal disorders Constipation	7.6% 13/170 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	6.5% 11/168 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	5.8% 10/171 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	8.5% 15/176 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	5.3% 9/169 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.
Gastrointestinal disorders Vomiting	6.5% 11/170 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	7.1% 12/168 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	7.6% 13/171 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	11.4% 20/176 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	2.4% 4/169 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.
Gastrointestinal disorders Flatulence	8.2% 14/170 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	7.1% 12/168 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	7.0% 12/171 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	8.0% 14/176 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	6.5% 11/169 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.
Nervous system disorders Dizziness	4.1% 7/170 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	5.4% 9/168 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	4.1% 7/171 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	11.9% 21/176 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	4.7% 8/169 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.
Nervous system disorders Somnolence	8.2% 14/170 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	3.6% 6/168 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	5.3% 9/171 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	7.4% 13/176 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	2.4% 4/169 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.
Nervous system disorders Headache	5.3% 9/170 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	3.0% 5/168 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	5.8% 10/171 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	5.7% 10/176 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	6.5% 11/169 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.
General disorders Pyrexia	8.8% 15/170 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	8.9% 15/168 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	9.4% 16/171 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	7.4% 13/176 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	9.5% 16/169 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.
Investigations Body temperature increased	2.4% 4/170 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	3.6% 6/168 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	4.1% 7/171 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	0.57% 1/176 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	5.9% 10/169 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.
Injury, poisoning and procedural complications Postoperative anemia	4.7% 8/170 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	3.0% 5/168 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	2.9% 5/171 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	2.3% 4/176 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.	5.9% 10/169 • Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events are reported.

Additional Information

Claudia Leinweber

Grunenthal GmbH

Phone: 49 241 569 2509

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 coordinating Investigator/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