Trial Outcomes & Findings for A Study to Evaluate the Effectiveness and Safety of Tapentadol (CG5503) in the Treatment of Acute Pain From Bunionectomy. (NCT NCT00613938)

NCT ID: NCT00613938

Last Updated: 2014-05-09

Results Overview

The SPID score incorporates the cumulative analgesic effects of tapentadol IR on pain intensity over an extended period (48 hours) allowing for an evaluation of multiple doses of drug, even when dosing frequency may vary. Scoring is derived from the Numerical Rating Scale (NRS) from 0 = No pain to 11 = Pain as bad as you can imagine. A positive difference between the mean SPID48 for an active study drug and placebo would indicate a numerically larger analgesic effect for subjects dosed with active study drug than in the placebo group. A higher value in SPID indicates greater pain relief.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 901 participants
• Primary outcome timeframe: 48 hours
• Results posted on: 2014-05-09

Participant Flow

The recruitment period for this inpatient, multicenter study occurred between January 28, 2008 and October 3, 2008.

The study consisted of a screening period (duration up to 28 days), and a double blind active treatment period (4 days).

Participant milestones

Measure	Placebo Placebo capsule taken by mouth every 4 to 6 hours for 3 days.	Tapentadol 50mg Fixed Dose Tapentadol 50mg capsule taken by mouth every 4 to 6 hours for 3 days.	Tapentadol 75mg Fixed Dose Tapentadol 75mg capsule taken by mouth every 4 to 6 hours for 3 days.	Oxycodone 10mg Fixed Dose Oxycodone 10mg capsule taken by mouth every 4 to 6 hours for 3 days.
Overall Study STARTED	69	275	278	279
Overall Study COMPLETED	49	247	255	253
Overall Study NOT COMPLETED	20	28	23	26

Reasons for withdrawal

Measure	Placebo Placebo capsule taken by mouth every 4 to 6 hours for 3 days.	Tapentadol 50mg Fixed Dose Tapentadol 50mg capsule taken by mouth every 4 to 6 hours for 3 days.	Tapentadol 75mg Fixed Dose Tapentadol 75mg capsule taken by mouth every 4 to 6 hours for 3 days.	Oxycodone 10mg Fixed Dose Oxycodone 10mg capsule taken by mouth every 4 to 6 hours for 3 days.
Overall Study Withdrawal by Subject	2	4	9	9
Overall Study Adverse Event	1	4	8	5
Overall Study Lack of Efficacy	16	18	5	9
Overall Study Other	1	2	1	3

Baseline Characteristics

A Study to Evaluate the Effectiveness and Safety of Tapentadol (CG5503) in the Treatment of Acute Pain From Bunionectomy.

Baseline characteristics by cohort

Measure	Placebo n=69 Participants Placebo capsule taken by mouth every 4 to 6 hours for 3 days.	Tapentadol 50mg Fixed Dose n=275 Participants Tapentadol 50mg capsule taken by mouth every 4 to 6 hours for 3 days.	Tapentadol 75mg Fixed Dose n=278 Participants Tapentadol 75mg capsule taken by mouth every 4 to 6 hours for 3 days.	Oxycodone 10mg Fixed Dose n=279 Participants Oxycodone 10mg capsule taken by mouth every 4 to 6 hours for 3 days.	Total n=901 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
Age, Categorical Between 18 and 65 years	68 participants n=5 Participants	265 participants n=7 Participants	268 participants n=5 Participants	265 participants n=4 Participants	866 participants n=21 Participants
Age, Categorical >=65 years	1 participants n=5 Participants	10 participants n=7 Participants	10 participants n=5 Participants	13 participants n=4 Participants	34 participants n=21 Participants
Age, Continuous	42.8 years STANDARD_DEVIATION 13.65 • n=5 Participants	42.4 years STANDARD_DEVIATION 13.23 • n=7 Participants	43.5 years STANDARD_DEVIATION 12.57 • n=5 Participants	43.4 years STANDARD_DEVIATION 13.25 • n=4 Participants	43.1 years STANDARD_DEVIATION 13.05 • n=21 Participants
Gender Female	64 participants n=5 Participants	232 participants n=7 Participants	248 participants n=5 Participants	233 participants n=4 Participants	777 participants n=21 Participants
Gender Male	5 participants n=5 Participants	43 participants n=7 Participants	30 participants n=5 Participants	45 participants n=4 Participants	123 participants n=21 Participants
Region of Enrollment United States	69 participants n=5 Participants	275 participants n=7 Participants	278 participants n=5 Participants	278 participants n=4 Participants	900 participants n=21 Participants

PRIMARY outcome

Timeframe: 48 hours

Population: The primary analysis set was the Intent to Treat (ITT) analysis set that included all subjects who were randomized, received at least one dose of study drug and had a non-missing baseline pain intensity score.

The SPID score incorporates the cumulative analgesic effects of tapentadol IR on pain intensity over an extended period (48 hours) allowing for an evaluation of multiple doses of drug, even when dosing frequency may vary. Scoring is derived from the Numerical Rating Scale (NRS) from 0 = No pain to 11 = Pain as bad as you can imagine. A positive difference between the mean SPID48 for an active study drug and placebo would indicate a numerically larger analgesic effect for subjects dosed with active study drug than in the placebo group. A higher value in SPID indicates greater pain relief.

Outcome measures

Measure	Placebo n=69 Participants Placebo capsule taken by mouth every 4 to 6 hours for 3 days.	Tapentadol 50mg Fixed Dose n=275 Participants Tapentadol 50mg capsule taken by mouth every 4 to 6 hours for 3 days.	Tapentadol 75mg Fixed Dose n=278 Participants Tapentadol 75mg capsule taken by mouth every 4 to 6 hours for 3 days.	Oxycodone 10mg Fixed Dose n=278 Participants Oxycodone 10mg capsule taken by mouth every 4 to 6 hours for 3 days.
Sum of Pain Intensity Difference Over 48 Hours (SPID48)	54.1 Scores on a scale Standard Deviation 105.74	122.2 Scores on a scale Standard Deviation 98.66	143.7 Scores on a scale Standard Deviation 96.52	140.3 Scores on a scale Standard Deviation 99.52

SECONDARY outcome

Timeframe: 3 days

Population: The primary analysis set was the Intent to Treat (ITT) analysis set that included all subjects who were randomized, received at least one dose of study drug and had a non-missing baseline pain intensity score.

The effect of tapentadol (CG5503) IR on the time to the first use of rescue pain medication.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 hours

Population: The primary analysis set was the Intent to Treat (ITT) analysis set that included all subjects who were randomized, received at least one dose of study drug and had a non-missing baseline pain intensity score.

The SPID score incorporates the cumulative analgesic effects of tapentadol IR on pain intensity over an extended period (12 to 72 hours) allowing for an evaluation of multiple doses of drug, even when dosing frequency may vary. Scoring is derived from the Numerical Rating Scale (NRS) from 0 = No pain to 11 = Pain as bad as you can imagine. A positive difference between the mean SPID12 for an active study drug and placebo would indicate a numerically larger analgesic effect for subjects dosed with active study drug than in the placebo group. A higher value in SPID indicates greater pain relief.

Outcome measures

Measure	Placebo n=69 Participants Placebo capsule taken by mouth every 4 to 6 hours for 3 days.	Tapentadol 50mg Fixed Dose n=275 Participants Tapentadol 50mg capsule taken by mouth every 4 to 6 hours for 3 days.	Tapentadol 75mg Fixed Dose n=278 Participants Tapentadol 75mg capsule taken by mouth every 4 to 6 hours for 3 days.	Oxycodone 10mg Fixed Dose n=278 Participants Oxycodone 10mg capsule taken by mouth every 4 to 6 hours for 3 days.
The SPID at 12 Hours Relative to First Dose.	7.5 Scores on a scale Standard Deviation 20.7	21.1 Scores on a scale Standard Deviation 21.89	26.0 Scores on a scale Standard Deviation 23.11	24.9 Scores on a scale Standard Deviation 22.8

SECONDARY outcome

Timeframe: 24 hours

Population: The primary analysis set was the Intent to Treat (ITT) analysis set that included all subjects who were randomized, received at least one dose of study drug and had a non-missing baseline pain intensity score.

The SPID score incorporates the cumulative analgesic effects of tapentadol IR on pain intensity over an extended period (12 to 72 hours) allowing for an evaluation of multiple doses of drug, even when dosing frequency may vary. Scoring is derived from the Numerical Rating Scale (NRS) from 0 = No pain to 11 = Pain as bad as you can imagine. A positive difference between the mean SPID24 for an active study drug and placebo would indicate a numerically larger analgesic effect for subjects dosed with active study drug than in the placebo group. A higher value in SPID indicates greater pain relief.

Outcome measures

Measure	Placebo n=69 Participants Placebo capsule taken by mouth every 4 to 6 hours for 3 days.	Tapentadol 50mg Fixed Dose n=275 Participants Tapentadol 50mg capsule taken by mouth every 4 to 6 hours for 3 days.	Tapentadol 75mg Fixed Dose n=278 Participants Tapentadol 75mg capsule taken by mouth every 4 to 6 hours for 3 days.	Oxycodone 10mg Fixed Dose n=278 Participants Oxycodone 10mg capsule taken by mouth every 4 to 6 hours for 3 days.
SPID at 24 Hours Relative to First Dose	12.1 Scores on a scale Standard Deviation 43.64	45.4 Scores on a scale Standard Deviation 45.73	58.1 Scores on a scale Standard Deviation 45.89	53.8 Scores on a scale Standard Deviation 46.69

SECONDARY outcome

Timeframe: Baseline and 3 days

Population: The primary analysis set was the Intent to Treat (ITT) analysis set that included all subjects who were randomized, received at least one dose of study drug and had a non-missing baseline pain intensity score.

Ordinal measure indicating change from the start of treatment (On a scale of 7 = Very much Worse to 1 = very much improved) to endpoint at Day 3

Outcome measures

Measure	Placebo n=69 Participants Placebo capsule taken by mouth every 4 to 6 hours for 3 days.	Tapentadol 50mg Fixed Dose n=275 Participants Tapentadol 50mg capsule taken by mouth every 4 to 6 hours for 3 days.	Tapentadol 75mg Fixed Dose n=278 Participants Tapentadol 75mg capsule taken by mouth every 4 to 6 hours for 3 days.	Oxycodone 10mg Fixed Dose n=278 Participants Oxycodone 10mg capsule taken by mouth every 4 to 6 hours for 3 days.
Percentage of Patients Who Reported Very Much Improved or Much Improved From Baseline in Patient Global Impression of Change to Day 3	65.2 percentage of participants	83.2 percentage of participants	87.8 percentage of participants	86.0 percentage of participants

SECONDARY outcome

Timeframe: 48 hours

Population: Intent-to-treat

Total Pain Relief (TOTPAR48) was defined as the weighted sum over all pain relief scores(PAR) from 0.5 hour to Hour 48, with the actual time elapsed from the previous PAR observation as the weight. A higher value in TOTPAR indicates greater pain relief.

Outcome measures

Measure	Placebo n=69 Participants Placebo capsule taken by mouth every 4 to 6 hours for 3 days.	Tapentadol 50mg Fixed Dose n=275 Participants Tapentadol 50mg capsule taken by mouth every 4 to 6 hours for 3 days.	Tapentadol 75mg Fixed Dose n=278 Participants Tapentadol 75mg capsule taken by mouth every 4 to 6 hours for 3 days.	Oxycodone 10mg Fixed Dose n=278 Participants Oxycodone 10mg capsule taken by mouth every 4 to 6 hours for 3 days.
Total Pain Relief (TOTPAR)at 48 Hours	68.2 scores on a scale Standard Deviation 39.48	96.6 scores on a scale Standard Deviation 37.39	107.5 scores on a scale Standard Deviation 35.74	105.2 scores on a scale Standard Deviation 37.4

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

Tapentadol 50mg Fixed Dose

Serious events: 0 serious events

Other events: 161 other events

Deaths: 0 deaths

Tapentadol 75mg Fixed Dose

Serious events: 0 serious events

Other events: 192 other events

Deaths: 0 deaths

Oxycodone 10mg Fixed Dose

Serious events: 1 serious events

Other events: 218 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=69 participants at risk Placebo capsule taken by mouth every 4 to 6 hours for 3 days.	Tapentadol 50mg Fixed Dose n=275 participants at risk Tapentadol 50mg capsule taken by mouth every 4 to 6 hours for 3 days.	Tapentadol 75mg Fixed Dose n=278 participants at risk Tapentadol 75mg capsule taken by mouth every 4 to 6 hours for 3 days.	Oxycodone 10mg Fixed Dose n=279 participants at risk Oxycodone 10mg capsule taken by mouth every 4 to 6 hours for 3 days.
Vascular disorders Deep vein thrombosis	0.00% 0/69 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	0.00% 0/275 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	0.00% 0/278 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	0.36% 1/279 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.

Other adverse events

Measure	Placebo n=69 participants at risk Placebo capsule taken by mouth every 4 to 6 hours for 3 days.	Tapentadol 50mg Fixed Dose n=275 participants at risk Tapentadol 50mg capsule taken by mouth every 4 to 6 hours for 3 days.	Tapentadol 75mg Fixed Dose n=278 participants at risk Tapentadol 75mg capsule taken by mouth every 4 to 6 hours for 3 days.	Oxycodone 10mg Fixed Dose n=279 participants at risk Oxycodone 10mg capsule taken by mouth every 4 to 6 hours for 3 days.
Investigations Alanine aminotransferase increased	1.4% 1/69 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	2.9% 8/275 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	2.5% 7/278 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	5.0% 14/279 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.
Gastrointestinal disorders Constipation	1.4% 1/69 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	8.0% 22/275 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	5.4% 15/278 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	11.1% 31/279 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.
Nervous system disorders Dizziness	10.1% 7/69 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	14.9% 41/275 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	24.8% 69/278 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	23.3% 65/279 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.
Nervous system disorders Headache	15.9% 11/69 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	20.4% 56/275 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	18.7% 52/278 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	26.2% 73/279 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.
Gastrointestinal disorders Nausea	17.4% 12/69 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	33.8% 93/275 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	45.7% 127/278 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	57.3% 160/279 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.
Skin and subcutaneous tissue disorders Pruritus	2.9% 2/69 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	5.1% 14/275 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	8.3% 23/278 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	10.0% 28/279 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.
Nervous system disorders Somnolence	2.9% 2/69 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	7.3% 20/275 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	13.3% 37/278 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	11.8% 33/279 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.
Gastrointestinal disorders Vomiting	0.00% 0/69 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	12.4% 34/275 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	27.7% 77/278 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.	25.8% 72/279 • All adverse events (AEs) were recorded from the time that the informed consent (ICF) was obtained until the last study procedure had been completed. For subjects who discontinued early, AEs were collected for 48 hours after the last intake of study drug.

Additional Information

Senior Director, Clinical Leader

Johnson & Johnson Pharmaceutical Research & Development

Phone: 609-730-4537

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60