Intravenous Tapentadol in Post-Bunionectomy Pain

Phase 2

Completed

Conditions: Bunion
Pain

Interventions: Drug: Matching Placebo
Drug: Tapentadol

Registration Number: NCT01435577

Lead Sponsor: Grünenthal GmbH

Brief Summary: The purpose of this trial is to established the safety and efficacy of multiple dose treatment with tapentadol IV in an adult population with moderate to severe pain following bunionectomy.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 177

Inclusion Criteria

Scheduled to undergo primary unilateral first metatarsal bunionectomy
Female patients must be postmenopausal, surgically sterile, or practicing an effective method of birth control if they are sexually active
Qualifying pain intensity (within a maximum of 5 hours after the last surgical stitch) and Baseline pain intensity (last pain score measured within 10 minutes before dosing) 5 on an 11-point (0 to 10) pain intensity numerical rating scale (NRS).

Exclusion Criteria

History of malignancy within the past 2 years
Current or history of alcohol or drug abuse.
Clinically relevant pulmonary, gastrointestinal, endocrine, metabolic, neurological, psychiatric disorders (resulting in disorientation, memory impairment or inability to report accurately
History of seizure disorder, epilepsy, or any condition that would put the subject at risk of seizures
Severely impaired renal function
Moderately or severely impaired hepatic function
Contraindications, or a history of allergy or hypersensitivity, to tapentadol, ibuprofen, or excipients
Use of prohibited concomitant medication, or not allowed use of restricted concomitant medication

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Matching placebo intravenous	Matching Placebo	Placebo (0.9% sodium chloride and water for injection). Ibuprofen 600 mg orally may be given as rescue medication for pain.
Tapentadol intravenous	Tapentadol	Tapentadol will be given by intravenous infusion. Tapentadol will be administered every 4 hours. Ibuprofen 600 mg orally may be given as rescue medication for pain not controlled by Tapentadol alone.

Primary Outcome Measures

Name	Time	Method
Sum of Pain Intensity Differences (SPID 24)	Baseline value; up to 24 hours after first study drug administration	Pain Intensity assessed at predefined time points (at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 20 and 24 hours after first drug administration) 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". Pain Intensity Differences at each predefined time point (calculated as post-baseline NRS values - baseline NRS values) were analyzed. Negative SPID24 values indicate a decrease in pain intensity and positive values indicate an increase in pain intensity since baseline.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With 50% Response After 24 Hours, Based on Pain Intensity Scores	Baseline value to 24 hours after first study drug administration	Individual participant response. Number of participants that reported a 50% or more reduction in pain intensity from the administration of the first dose to 24 hours after the first study drug administration are counted as having a response if their pain intensity decreased by 50% from their baseline value.
Pharmacokinetic Concentrations of Tapentadol-O-glucuronide	15 minutes to 20 hours after first drug administration	Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as "breakdown products". The body alters the administered medication to a metabolite so that can be more easily or quickly removed from the body. Tapentadol-O-glucuronide concentrations were measured in participants in the tapentadol treatment arm. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 0.2 ng/mL.
Sum of Pain Intensity Differences After 12 Hours	Baseline value to 12 hours after first study drug administration	Pain Intensity (PI) was assessed on 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine. Pain Intensity Difference (PID) was the difference between the PI after fixed times after first dose and the baseline PI (prior to the first dose). The Sum of Pain Intensity Differences over 12 hours was calculated. If the values are negative (then the baseline pain intensity was greater than the pain intensity measured after dosing).
Number of Participants With 30% Response After 24 Hours, Based on Pain Intensity Scores	Baseline value to 24 hours after first study drug administration	Individual participant response. Number of participants that reported a 30% or more reduction in pain intensity from the administration of the first dose to 24 hours after the first study drug administration are counted as having a response if their pain intensity decreased by 30% from their baseline value.
Mean Pain Intensity Scores at Fixed Time Points	Baseline; up to 48 hours	The mean pain intensity at fixed time points in the trial for all participants is listed. The pain intensity was measured using the Pain Intensity (PI). Pain intensity was assessed on 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine.
Patients Global Impression of Change After 24 Hours of Treatment	Baseline value to 24 hours after study drug administration	In the Patient Global Impression of Change (PGIC) the participant indicates the perceived change over the treatment period. The participant verbally rated their impression of overall status with 1 of 7 possible responses (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse).
Patient Global Impression of Change After 48 Hours of Treatment	Baseline value to 48 hours after first study drug administration	In the Patient Global Impression of Change (PGIC) the participant indicates the perceived change over the treatment period. The participant verbally rated their impression of overall status with 1 of 7 possible responses (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse).
Sum of Pain Intensity Differences After 4 Hours	Baseline value to 4 hours after first study drug intake	Pain Intensity (PI) was assessed on 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine. Pain Intensity Difference (PID) was the difference between the PI after fixed times after first dose and the baseline PI (prior to the first dose). The Sum of Pain Intensity Differences over 4 hours was calculated. If the values are negative (then the baseline pain intensity was greater than the pain intensity measured after dosing).
Sum of Pain Intensity Differences After 8 Hours	Baseline value to 8 hours after first study drug administration	Pain Intensity (PI) was assessed on 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine. Pain Intensity Difference (PID) was the difference between the PI after fixed times after first dose and the baseline PI (prior to the first dose). The Sum of Pain Intensity Differences over 8 hours was calculated. If the values are negative (then the baseline pain intensity was greater than the pain intensity measured after dosing).
Pain Intensity Differences at Fixed Time Points	Starting at 15 minutes and up to 48 hours after first drug administration	Pain Intensity (PI) was assessed on 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine. Pain Intensity Difference (PID) was the difference between baseline pain intensity (prior to the first dose) and the pain intensity at the time. A negative number indicates a decrease in pain in the whole treatment group. The greater the negative pain intensity difference value the greater the pain relief in the treatment arm. A score of 0 indicates that there has been no change in pain in a treatment group. A positive value indicates an increase in pain in the treatment group.
Sum of Pain Intensity Differences After 60 Minutes	Baseline value to 60 minutes after first study drug administration	Pain Intensity (PI) was assessed on 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine. Pain Intensity Difference (PID) was the difference between the PI after fixed times after first dose and the baseline PI (prior to the first dose). The Sum of Pain Intensity Differences over 60 minutes was calculated. If the value is negative then the baseline pain intensity was greater than the pain intensity measured after dosing.
Number of Participants With 30% Response After 12 Hours, Based on Pain Intensity Scores	Baseline value to 12 hours after first study drug administration	Individual participant response. Number of participants that reported a 30% or more reduction in pain intensity from the administration of the first dose to 12 hours after the first study drug administration are counted as having a response if their pain intensity decreased by 30% from their baseline value.
Number of Participants With 30% Response After 48 Hours, Based on Pain Intensity Scores	Baseline value to 48 hours after first study drug administration	Individual participants response. Number of participants that reported a 30% or more reduction in pain intensity from the administration of the first dose to 48 hours after the first study drug administration are counted as having a response if their pain intensity decreased by 30% from their baseline value.
Patient Global Impression of Change After 12 Hours of Treatment	Baseline value to 12 hours after first study drug administration	In the Patient Global Impression of Change (PGIC) the participant indicates the perceived change over the treatment period. The participant verbally rated their impression of overall status with 1 of 7 possible responses (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse).
Sum of Pain Intensity Differences After 48 Hours	Baseline value to 48 hours after first study drug administration	Pain Intensity (PI) was assessed on 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine. Pain Intensity Difference (PID) was the difference between the PI after fixed times after first dose and the baseline PI (prior to the first dose). The Sum of Pain Intensity Differences over 60 minutes was calculated. If the values are negative (then the baseline pain intensity was greater than the pain intensity measured after dosing).
Number of Participants With 50% Response After 12 Hours, Based on Pain Intensity Scores	Baseline value to 12 hours after first study drug administration	Individual participant response. Number of participants that reported a 50% or more reduction in pain intensity from the administration of the first dose to 12 hours after the first study drug administration are counted as having a response if their pain intensity decreased by 50% from their baseline value.
Number of Participants With 50% Response After 48 Hours, Based on Pain Intensity Scores	Baseline value to 48 hours after first study drug administration	Individual participant response. Number of participants that reported a 50% or more reduction in pain intensity from the administration of the first dose to 48 hours after the first study drug administration are counted as having a response if their pain intensity decreased by 50% from their baseline value.
Time to First Rescue Medication	up to 48 hours	The median time to first rescue medication intake (600 mg ibuprofen) in hours.
Time to Meaningful Pain Relief	up to 48 hours	The participant was instructed to stop the stopwatch when they had meaningful pain relief. That is, when the pain relief made a real difference, after the first drug administration.
Time to Perceptible Pain Relief	up to 48 hours	When the participant began to feel any pain-relieving effect after the administration of the first dose they were requested to stop the first stopwatch. The time was noted. This measured when the participant first felt any difference in the pain.
Pharmacokinetic Concentrations of Tapentadol	15 minutes to 20 hours after first drug administration	Tapentadol concentrations were measured in participants in the tapentadol treatment arm. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 0.2 ng/mL.
Mean Pain Intensity Scores at Relative Time- Tapentadol Randomized Participants	Baseline; for the first 6 administrations	The pain intensity at the relative time points are the pain intensity before and one hour after study drug administration. The pain intensity was measured using the Pain Intensity (PI). Pain intensity was assessed on 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine.
Mean Pain Intensity Scores at Relative Time - Matching Placebo Randomized Participants	Baseline; for the first 6 administrations	The pain intensity at the relative time points are the pain intensity before and one hour after study drug administration. The pain intensity was measured using the Pain Intensity (PI). Pain intensity was assessed on 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine.