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Efficacy and Safety of IV Diclofenac (DIV075V)for Pain After Elective Orthopedic Surgery

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00507026
Collaborator
(none)
277
Enrollment
8
Locations
3
Arms
14.7
Actual Duration (Months)
34.6
Patients Per Site
2.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will compare repeated intermittent IV dosing of diclofenac in patient with moderate to severe post-surgical pain from elective orthopedic surgery.

Condition or Disease Intervention/Treatment Phase
  • Drug: IV Diclofenac
  • Drug: IV ketorolac
  • Drug: Placebo
 Phase 3

Detailed Description

The primary objective is to evaluate the analgesic efficacy and safety of three dosage levels of parenteral diclofenac in providing pain relief as compared to placebo or Ketorolac tromethamine.

Study Design

Study Type:
Interventional
Actual Enrollment :
277 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Randomized, Double-Blind, Active-and Placebo-Controlled Study of the Analgesic Efficacy and Safety of Repeated Dosing of DIC075V Versus Parenteral Ketorolac and Placebo in Acute Post-Operative Pain After Elective Orthopedic Surgery
Actual Study Start Date :
Jul 25, 2007
Actual Primary Completion Date :
Oct 14, 2008
Actual Study Completion Date :
Oct 14, 2008

Arms and Interventions

Arm Intervention/Treatment
Experimental: A

DIC075V (IV diclofenac)

Drug: IV Diclofenac
IV Diclofenac q6h
Active Comparator: B

IV Ketorolac

Drug: IV ketorolac
IV ketorolac q6h
Placebo Comparator: C

Placebo

Drug: Placebo
Placebo q6h

Outcome Measures

Primary Outcome Measures

  1. Sum of the Pain Intensity Differences (SPID) Over 24 Hours [Over 24 hours post first dose]

    Pain intensity was measured on VAS (from 0 mm to 100 mm: 0 = no pain, 100 = worst possible pain). For each post dose time point, pain intensity difference (PID) is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement. SPIDs was calculated by multiplying the PID score at each post-dose time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. SPID over 24 hours ranges from -2400 to 2400. A higher value indicates a better pain reduction.

  2. Sum of the Pain Intensity Differences (SPID) Over 48 Hours [Over 48 hours post first dose]

    Pain intensity was measured on VAS (from 0 mm to 100 mm: 0 = no pain, 100 = worst possible pain). For each post dose time point, PID is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement. SPIDs was calculated by multiplying the PID score at each post-dose time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. SPID over 48 hours ranges from -4800 to 4800. A higher value indicates a better pain reduction.

  3. Sum of the Pain Intensity Differences (SPID) Over 72 Hours [Over 72 hours post first dose]

    Pain intensity was measured on VAS (from 0 mm to 100 mm: 0 = no pain, 100 = worst possible pain). For each post dose time point, PID is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement. SPIDs was calculated by multiplying the PID score at each post-dose time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. SPID over 72 hours ranges from -7200 to 7200. A higher value indicates a better pain reduction.

  4. Sum of the Pain Intensity Differences (SPID) Over 96 Hours [Over 96 hours post first dose]

    Pain intensity was measured on VAS (from 0 mm to 100 mm: 0 = no pain, 100 = worst possible pain). For each post dose time point, PID is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement. SPIDs was calculated by multiplying the PID score at each post-dose time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. SPID over 96 hours ranges from -9600 to 9600. A higher value indicates a better pain reduction.

  5. Sum of the Pain Intensity Differences (SPID) Over 120 Hours [Over 120 hours post first dose]

    Pain intensity was measured on VAS (from 0 mm to 100 mm: 0 = no pain, 100 = worst possible pain). For each post dose time point, PID is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement. SPIDs was calculated by multiplying the PID score at each post-dose time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. SPID over 120 hours ranges from -12000 to 12000. A higher value indicates a better pain reduction.

Secondary Outcome Measures

  1. Pain Intensity Differences (PID) Over Time [Baseline (0 hour), 5, 10, 15, 30, 45 minutes post first dose, 1, 2, 3, 5, 6, 9, 12, 15, 18, 21, 24, 48, 72, 96, 120 hours post first dose]

    Pain intensity was measured on VAS (from 0 mm to 100 mm: 0 = no pain, 100 = worst possible pain). For each post dose time point, PID is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). PID score range at any post dose (post baseline) evaluation time point was -100 to 100. A positive difference score is indicative of improvement.

  2. Percentage of Participants Attaining Greater Than or Equal to (>=) 30 Percent (%) Reduction From Baseline in Pain Intensity [Baseline (0 hour), 5, 30 minutes post first dose, 1, 24, 48, 72, 90, 120 hours post first dose]

    Pain intensity was measured on a 0 to 100 mm VAS, larger values indicate greater pain intensity. In this outcome measure, percentage of participants attaining >= 30 % reduction in pain intensity from baseline to specified time points was reported.

  3. Total Pain Relief (TOTPAR) [0-24, 0-48, 0-72, 0-96 and 0-120 hours post first dose]

    Pain relief values at specified time points were measured on a 0 to 100 mm VAS, where higher values indicate greater pain relief. TOTPAR over specified time interval was calculated as area under pain relief curve over specified time intervals using trapezoidal approximation. For 0-24 hours score range was 0-2400, for 0-48 hours score range was 0- 4800, for 0-96 hours score range was 0-9600 and for 0-120 hours score range was 0-12000. Higher TOTPAR values indicated more relief.

  4. Visual Analog Pain Relief Values Over the Time [5, 10, 15, 30, 45 minutes post first dose, 1, 2, 3, 5, 6, 9, 12, 15, 18, 21, 24, 48, 72, 96, 120 hours post first dose]

    Pain relief values at specified time points were measured on a 0 to 100 mm VAS, where higher values indicate greater pain relief.

  5. Time From Administration of Study Drug to Administration of Rescue Medication [Maximum up to 5 days]

    Time from administration of study drug to administration of rescue medication were censored at time of last pain assessment for participants who did not receive rescue medication. Rescue medication was additional pain medication, available to participants if they did not receive pain relief from the study drug. Rescue medication available during this study was IV morphine.

  6. Cumulative Amount of Rescue Medication [0-24, 0-48, 0-72, 0-96 and 0-120 hours]

    In this outcome measure, cumulative amount of rescue medication used over 0-24, 0-48, 0-72, 0-96, and 0-120 hours were reported. Rescue medication was additional pain medication, available to participants if they did not receive pain relief from the study drug. Rescue medication available during this study was IV morphine.

  7. Number of Participants According to Frequency of Use of Rescue Medication [0-24, 0-48, 0-72, 0-96 and 0-120 hours post first dose]

    In this outcome measure, number of participants are reported according to number of times they received rescue medication. Rescue medication was additional pain medication, available to participants if they did not receive pain relief from the study drug. Rescue medication available during this study was IV morphine. Only those categories with at least one nonzero value are reported.

  8. Participant Global Evaluation Over Time [0-24, 0-48, 0-120 hours post-dose]

    Participants global evaluation of study medication was accessed on a scale ranging from scale 0 to 4 where 0= poor, 1= fair, 2= good, 3= very good, 4= excellent where higher score represented better outcome.

  9. Time to Perceptible Relief [Within 6 hours of first dose on Day 1]

    Participants were instructed to stop the first stopwatch at the onset of perceptible pain relief after first dose. Event times of participants not reporting perceptible relief were censored at 6 hours; event times of participants who withdrew or were administered rescue medication were censored at time of withdrawal or rescue. Kaplan-Meier estimate was used for analysis.

  10. Time to Meaningful Relief [Within 6 hours of first dose on Day 1]

    Participants were instructed to stop the second stopwatch at the onset of meaningful pain relief after first dose. Event times of participants not reporting meaningful relief were censored at 6 hours; event times of participants who withdrew or were administered rescue medication were censored at time of withdrawal or rescue. Kaplan-Meier estimate was used for analysis.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 85 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Scheduled within three weeks of the screening visit to undergo elective orthopedic surgery.

  • Moderate to severe pain within 6 hours following completion of the required surgery.

Exclusion Criteria:

  • Chronic pain conditions.

  • Chronic disease or recent cardiovascular events.

  • Known allergy or hypersensitivity to the active compounds or any of the excipients used in the study.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Helen Keller Hospital Sheffield Alabama United States 35660
2 Arizona Research Center Phoenix Arizona United States 85023
3 Accurate Clinical Trials San Clemente California United States 92672
4 East Coast Clincial Research Fort Pierce Florida United States 34950
5 Outcomes Research Institute Louisville Kentucky United States 40202
6 American Institute of Healthcare and Fitness Raleigh North Carolina United States 27615
7 University Orthopedics Center State College Pennsylvania United States 16081
8 SCIREX Austin Texas United States 78705

Sponsors and Collaborators

  • Pfizer

Investigators

  • Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00507026
Other Study ID Numbers:
  • DFC-005
  • C1211009
First Posted:
Jul 25, 2007
Last Update Posted:
Oct 29, 2021
Last Verified:
Sep 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Additional relevant MeSH terms:
Pain, Postoperative
Diclofenac
Ketorolac

Study Results

Participant Flow

Recruitment Details Participants who required elective general orthopedic surgery were eligible for participation in this study. Within 6 hours after completion of surgery, participants who experienced moderate to severe pain, as measured by a 0-100 millimeter (mm) visual analog scale (VAS) with pain intensity (PI) score of greater than or equal to (>=) 50 mm and who met all eligibility criteria were enrolled into the study.
Pre-assignment Detail Total 432 participants signed the inform consent form (ICF). Out of which 155 participants were not admitted into the study, 277 actually enrolled into the study and assigned to study treatment.
Arm/Group Title Diclofenac (DIC075V) Ketorolac Placebo
Arm/Group Description Participants at high risk (weighing less than [<] 50 killogram [k]), age >= 65 years, elevated nonsteroidal anti-inflammatory drugs [NSAID]-related gastrointestinal [GI] risk factors, or with hepatic or renal impairment) received DIC075V 18.75 milligram (mg). Participants without any risk factor and weighing greater than (>) 95 kg received DIC075V 50 mg. Participants weighing >95 kg with any risk factor received DIC075V 18.75 mg. All other participants received DIC075V 37.5 mg. DIC075V was administered as intravenous (IV) bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants at high risk (weighing <50 k, >=65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received ketorolac tromethamine 15 mg. Participants without any risk factor and weighing >95 kg received ketorolac tromethamine 30 mg. Participants weighing >95 kg with any risk factor received ketorolac tromethamine 15 mg. All other participants received ketorolac tromethamine 30 mg. Ketorolac tromethamine was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants received saline as placebo as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration.
Period Title: Overall Study
STARTED 145 60 72
COMPLETED 132 56 51
NOT COMPLETED 13 4 21

Baseline Characteristics

Arm/Group Title Diclofenac (DIC075V) Ketorolac Placebo Total
Arm/Group Description Participants at high risk (weighing <50 k), age >= 65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received DIC075V 18.75 mg. Participants without any risk factor and weighing >95 kg received DIC075V 50 mg. Participants weighing >95 kg with any risk factor received DIC075V 18.75 mg. All other participants received DIC075V 37.5 mg. DIC075V was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants at high risk (weighing <50 k, >=65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received ketorolac tromethamine 15 mg. Participants without any risk factor and weighing >95 kg received ketorolac tromethamine 30 mg. Participants weighing >95 kg with any risk factor received ketorolac tromethamine 15 mg. All other participants received ketorolac tromethamine 30 mg. Ketorolac tromethamine was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants received saline as placebo as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Total of all reporting groups
Overall Participants 145 60 72 277
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
55.9
(14.35)
54.9
(15.77)
54.5
(15.67)
55.3
(14.97)
Sex: Female, Male (Count of Participants)
Female
92
63.4%
40
66.7%
46
63.9%
178
64.3%
Male
53
36.6%
20
33.3%
26
36.1%
99
35.7%

Outcome Measures

1. Primary Outcome
Title Sum of the Pain Intensity Differences (SPID) Over 24 Hours
Description Pain intensity was measured on VAS (from 0 mm to 100 mm: 0 = no pain, 100 = worst possible pain). For each post dose time point, pain intensity difference (PID) is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement. SPIDs was calculated by multiplying the PID score at each post-dose time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. SPID over 24 hours ranges from -2400 to 2400. A higher value indicates a better pain reduction.
Time Frame Over 24 hours post first dose

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized into the study and who received at least 1 dose of study medication.
Arm/Group Title Diclofenac (DIC075V) Ketorolac Placebo
Arm/Group Description Participants at high risk (weighing <50 k), age >= 65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received DIC075V 18.75 mg. Participants without any risk factor and weighing >95 kg received DIC075V 50 mg. Participants weighing >95 kg with any risk factor received DIC075V 18.75 mg. All other participants received DIC075V 37.5 mg. DIC075V was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants at high risk (weighing <50 k, >=65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received ketorolac tromethamine 15 mg. Participants without any risk factor and weighing >95 kg received ketorolac tromethamine 30 mg. Participants weighing >95 kg with any risk factor received ketorolac tromethamine 15 mg. All other participants received ketorolac tromethamine 30 mg. Ketorolac tromethamine was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants received saline as placebo as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration.
Measure Participants 145 60 72
Mean (Standard Deviation) [mm*hours]
577.0
(570.90)
563.2
(586.21)
28.0
(428.43)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Diclofenac (DIC075V), Placebo
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method ANCOVA
Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ketorolac, Placebo
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method ANCOVA
Comments
2. Primary Outcome
Title Sum of the Pain Intensity Differences (SPID) Over 48 Hours
Description Pain intensity was measured on VAS (from 0 mm to 100 mm: 0 = no pain, 100 = worst possible pain). For each post dose time point, PID is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement. SPIDs was calculated by multiplying the PID score at each post-dose time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. SPID over 48 hours ranges from -4800 to 4800. A higher value indicates a better pain reduction.
Time Frame Over 48 hours post first dose

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized into the study and who received at least 1 dose of study medication.
Arm/Group Title Diclofenac (DIC075V) Ketorolac Placebo
Arm/Group Description Participants at high risk (weighing <50 k), age >= 65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received DIC075V 18.75 mg. Participants without any risk factor and weighing >95 kg received DIC075V 50 mg. Participants weighing >95 kg with any risk factor received DIC075V 18.75 mg. All other participants received DIC075V 37.5 mg. DIC075V was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants at high risk (weighing <50 k, >=65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received ketorolac tromethamine 15 mg. Participants without any risk factor and weighing >95 kg received ketorolac tromethamine 30 mg. Participants weighing >95 kg with any risk factor received ketorolac tromethamine 15 mg. All other participants received ketorolac tromethamine 30 mg. Ketorolac tromethamine was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants received saline as placebo as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration.
Measure Participants 145 60 72
Mean (Standard Deviation) [mm*hours]
1527.5
(1139.30)
1371.8
(1152.19)
400.4
(949.54)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Diclofenac (DIC075V), Placebo
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method ANCOVA
Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ketorolac, Placebo
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method ANCOVA
Comments
3. Primary Outcome
Title Sum of the Pain Intensity Differences (SPID) Over 72 Hours
Description Pain intensity was measured on VAS (from 0 mm to 100 mm: 0 = no pain, 100 = worst possible pain). For each post dose time point, PID is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement. SPIDs was calculated by multiplying the PID score at each post-dose time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. SPID over 72 hours ranges from -7200 to 7200. A higher value indicates a better pain reduction.
Time Frame Over 72 hours post first dose

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized into the study and who received at least 1 dose of study medication.
Arm/Group Title Diclofenac (DIC075V) Ketorolac Placebo
Arm/Group Description Participants at high risk (weighing <50 k), age >= 65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received DIC075V 18.75 mg. Participants without any risk factor and weighing >95 kg received DIC075V 50 mg. Participants weighing >95 kg with any risk factor received DIC075V 18.75 mg. All other participants received DIC075V 37.5 mg. DIC075V was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants at high risk (weighing <50 k, >=65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received ketorolac tromethamine 15 mg. Participants without any risk factor and weighing >95 kg received ketorolac tromethamine 30 mg. Participants weighing >95 kg with any risk factor received ketorolac tromethamine 15 mg. All other participants received ketorolac tromethamine 30 mg. Ketorolac tromethamine was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants received saline as placebo as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration.
Measure Participants 145 60 72
Mean (Standard Deviation) [mm*hours]
2592.1
(1730.92)
2312.1
(1743.73)
836.8
(1564.24)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Diclofenac (DIC075V), Placebo
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method ANCOVA
Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ketorolac, Placebo
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method ANCOVA
Comments
4. Primary Outcome
Title Sum of the Pain Intensity Differences (SPID) Over 96 Hours
Description Pain intensity was measured on VAS (from 0 mm to 100 mm: 0 = no pain, 100 = worst possible pain). For each post dose time point, PID is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement. SPIDs was calculated by multiplying the PID score at each post-dose time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. SPID over 96 hours ranges from -9600 to 9600. A higher value indicates a better pain reduction.
Time Frame Over 96 hours post first dose

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized into the study and who received at least 1 dose of study medication.
Arm/Group Title Diclofenac (DIC075V) Ketorolac Placebo
Arm/Group Description Participants at high risk (weighing <50 k), age >= 65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received DIC075V 18.75 mg. Participants without any risk factor and weighing >95 kg received DIC075V 50 mg. Participants weighing >95 kg with any risk factor received DIC075V 18.75 mg. All other participants received DIC075V 37.5 mg. DIC075V was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants at high risk (weighing <50 k, >=65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received ketorolac tromethamine 15 mg. Participants without any risk factor and weighing >95 kg received ketorolac tromethamine 30 mg. Participants weighing >95 kg with any risk factor received ketorolac tromethamine 15 mg. All other participants received ketorolac tromethamine 30 mg. Ketorolac tromethamine was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants received saline as placebo as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration.
Measure Participants 145 60 72
Mean (Standard Deviation) [mm*hours]
3711.3
(2347.25)
3331.9
(2356.36)
1337.8
(2261.50)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Diclofenac (DIC075V), Placebo
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method ANCOVA
Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ketorolac, Placebo
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method ANCOVA
Comments
5. Primary Outcome
Title Sum of the Pain Intensity Differences (SPID) Over 120 Hours
Description Pain intensity was measured on VAS (from 0 mm to 100 mm: 0 = no pain, 100 = worst possible pain). For each post dose time point, PID is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement. SPIDs was calculated by multiplying the PID score at each post-dose time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. SPID over 120 hours ranges from -12000 to 12000. A higher value indicates a better pain reduction.
Time Frame Over 120 hours post first dose

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized into the study and who received at least 1 dose of study medication.
Arm/Group Title Diclofenac (DIC075V) Ketorolac Placebo
Arm/Group Description Participants at high risk (weighing <50 k), age >= 65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received DIC075V 18.75 mg. Participants without any risk factor and weighing >95 kg received DIC075V 50 mg. Participants weighing >95 kg with any risk factor received DIC075V 18.75 mg. All other participants received DIC075V 37.5 mg. DIC075V was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants at high risk (weighing <50 k, >=65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received ketorolac tromethamine 15 mg. Participants without any risk factor and weighing >95 kg received ketorolac tromethamine 30 mg. Participants weighing >95 kg with any risk factor received ketorolac tromethamine 15 mg. All other participants received ketorolac tromethamine 30 mg. Ketorolac tromethamine was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants received saline as placebo as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration.
Measure Participants 145 60 72
Mean (Standard Deviation) [mm*hours]
4835.6
(2988.78)
4359.1
(3001.32)
1840.5
(2987.85)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Diclofenac (DIC075V), Placebo
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method ANCOVA
Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ketorolac, Placebo
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method ANCOVA
Comments
6. Secondary Outcome
Title Pain Intensity Differences (PID) Over Time
Description Pain intensity was measured on VAS (from 0 mm to 100 mm: 0 = no pain, 100 = worst possible pain). For each post dose time point, PID is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). PID score range at any post dose (post baseline) evaluation time point was -100 to 100. A positive difference score is indicative of improvement.
Time Frame Baseline (0 hour), 5, 10, 15, 30, 45 minutes post first dose, 1, 2, 3, 5, 6, 9, 12, 15, 18, 21, 24, 48, 72, 96, 120 hours post first dose

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized into the study and who received at least 1 dose of study medication. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "number analyzed" signifies participants evaluable at specific time points.
Arm/Group Title Diclofenac (DIC075V) Ketorolac Placebo
Arm/Group Description Participants at high risk (weighing <50 k), age >= 65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received DIC075V 18.75 mg. Participants without any risk factor and weighing >95 kg received DIC075V 50 mg. Participants weighing >95 kg with any risk factor received DIC075V 18.75 mg. All other participants received DIC075V 37.5 mg. DIC075V was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants at high risk (weighing <50 k, >=65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received ketorolac tromethamine 15 mg. Participants without any risk factor and weighing >95 kg received ketorolac tromethamine 30 mg. Participants weighing >95 kg with any risk factor received ketorolac tromethamine 15 mg. All other participants received ketorolac tromethamine 30 mg. Ketorolac tromethamine was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants received saline as placebo as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration.
Measure Participants 144 60 71
At 5 minutes
5.2
(14.27)
3.2
(15.85)
1.2
(15.21)
At 10 minutes
9.1
(19.36)
5.5
(19.61)
2.4
(21.46)
At 15 minutes
13.4
(22.06)
9.8
(23.21)
2.2
(25.41)
At 30 minutes
17.7
(24.36)
16.7
(23.22)
2.6
(30.16)
At 45 minutes
18.5
(27.12)
18.4
(27.56)
-1.2
(30.15)
At 1 hour
18.7
(28.54)
19.7
(31.60)
-4.2
(28.03)
At 2 hours
17.3
(30.22)
16.9
(32.81)
-7.8
(23.86)
At 3 hours
13.5
(29.30)
14.7
(32.94)
-8.9
(19.21)
At 5 hours
10.8
(30.11)
15.1
(32.01)
-7.3
(20.76)
At 6 hours
12.6
(31.05)
12.5
(29.69)
-6.1
(21.31)
At 9 hours
23.6
(32.07)
21.3
(33.34)
-1.8
(22.91)
At 12 hours
23.4
(31.83)
23.7
(32.44)
1.4
(24.75)
At 15 hours
28.5
(31.34)
23.2
(35.19)
1.1
(25.35)
At 18 hours
30.2
(32.27)
30.1
(32.80)
8.7
(24.16)
At 21 hours
36.3
(31.03)
39.1
(32.41)
8.8
(26.66)
At 24 hours
31.8
(32.47)
27.5
(32.96)
12.9
(26.38)
At 48 hours
42.9
(29.17)
35.5
(30.38)
19.4
(29.69)
At 72 hours
47.0
(27.65)
41.0
(30.40)
20.3
(31.44)
At 96 hours
46.8
(28.42)
43.0
(28.92)
At 120 hours
46.9
(28.42)
42.9
(28.91)
20.9
(31.48)
7. Secondary Outcome
Title Percentage of Participants Attaining Greater Than or Equal to (>=) 30 Percent (%) Reduction From Baseline in Pain Intensity
Description Pain intensity was measured on a 0 to 100 mm VAS, larger values indicate greater pain intensity. In this outcome measure, percentage of participants attaining >= 30 % reduction in pain intensity from baseline to specified time points was reported.
Time Frame Baseline (0 hour), 5, 30 minutes post first dose, 1, 24, 48, 72, 90, 120 hours post first dose

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized into the study and who received at least 1 dose of study medication.
Arm/Group Title Diclofenac (DIC075V) Ketorolac Placebo
Arm/Group Description Participants at high risk (weighing <50 k), age >= 65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received DIC075V 18.75 mg. Participants without any risk factor and weighing >95 kg received DIC075V 50 mg. Participants weighing >95 kg with any risk factor received DIC075V 18.75 mg. All other participants received DIC075V 37.5 mg. DIC075V was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants at high risk (weighing <50 k, >=65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received ketorolac tromethamine 15 mg. Participants without any risk factor and weighing >95 kg received ketorolac tromethamine 30 mg. Participants weighing >95 kg with any risk factor received ketorolac tromethamine 15 mg. All other participants received ketorolac tromethamine 30 mg. Ketorolac tromethamine was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants received saline as placebo as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration.
Measure Participants 145 60 72
At 5 minutes
13.8
9.5%
10.0
16.7%
8.3
11.5%
At 30 minutes
43.4
29.9%
35.0
58.3%
25.0
34.7%
At 1 hour
44.8
30.9%
41.7
69.5%
15.3
21.3%
At 24 hours
62.1
42.8%
56.7
94.5%
31.09
43.2%
At 48 hours
75.2
51.9%
63.3
105.5%
41.7
57.9%
At 72 hours
80.0
55.2%
71.7
119.5%
41.7
57.9%
At 90 hours
80.0
55.2%
75.0
125%
43.1
59.9%
At 120 hours
80.7
55.7%
75.0
125%
43.1
59.9%
8. Secondary Outcome
Title Total Pain Relief (TOTPAR)
Description Pain relief values at specified time points were measured on a 0 to 100 mm VAS, where higher values indicate greater pain relief. TOTPAR over specified time interval was calculated as area under pain relief curve over specified time intervals using trapezoidal approximation. For 0-24 hours score range was 0-2400, for 0-48 hours score range was 0- 4800, for 0-96 hours score range was 0-9600 and for 0-120 hours score range was 0-12000. Higher TOTPAR values indicated more relief.
Time Frame 0-24, 0-48, 0-72, 0-96 and 0-120 hours post first dose

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized into the study and who received at least 1 dose of study medication.
Arm/Group Title Diclofenac (DIC075V) Ketorolac Placebo
Arm/Group Description Participants at high risk (weighing <50 k), age >= 65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received DIC075V 18.75 mg. Participants without any risk factor and weighing >95 kg received DIC075V 50 mg. Participants weighing >95 kg with any risk factor received DIC075V 18.75 mg. All other participants received DIC075V 37.5 mg. DIC075V was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants at high risk (weighing <50 k, >=65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received ketorolac tromethamine 15 mg. Participants without any risk factor and weighing >95 kg received ketorolac tromethamine 30 mg. Participants weighing >95 kg with any risk factor received ketorolac tromethamine 15 mg. All other participants received ketorolac tromethamine 30 mg. Ketorolac tromethamine was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants received saline as placebo as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration.
Measure Participants 145 60 72
0-24 hours
1177.6
(611.13)
1065.4
(616.28)
484.7
(502.91)
0-48 hours
2768.3
(1239.29)
2453.8
(1323.35)
1327.9
(1258.96)
0-72 hours
4471.0
(1898.89)
3983.6
(2056.63)
2214.6
(2103.25)
0-96 hours
6252.2
(2577.46)
5575.7
(2828.49)
3159.4
(3002.62)
0-120 hours
8042.5
(3282.39)
7178.0
(3627.97)
4105.4
(3922.22)
9. Secondary Outcome
Title Visual Analog Pain Relief Values Over the Time
Description Pain relief values at specified time points were measured on a 0 to 100 mm VAS, where higher values indicate greater pain relief.
Time Frame 5, 10, 15, 30, 45 minutes post first dose, 1, 2, 3, 5, 6, 9, 12, 15, 18, 21, 24, 48, 72, 96, 120 hours post first dose

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized into the study and who received at least 1 dose of study medication.
Arm/Group Title Diclofenac (DIC075V) Ketorolac Placebo
Arm/Group Description Participants at high risk (weighing <50 k), age >= 65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received DIC075V 18.75 mg. Participants without any risk factor and weighing >95 kg received DIC075V 50 mg. Participants weighing >95 kg with any risk factor received DIC075V 18.75 mg. All other participants received DIC075V 37.5 mg. DIC075V was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants at high risk (weighing <50 k, >=65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received ketorolac tromethamine 15 mg. Participants without any risk factor and weighing >95 kg received ketorolac tromethamine 30 mg. Participants weighing >95 kg with any risk factor received ketorolac tromethamine 15 mg. All other participants received ketorolac tromethamine 30 mg. Ketorolac tromethamine was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants received saline as placebo as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration.
Measure Participants 145 60 72
At 5 minutes
21.9
(25.27)
17.9
(25.26)
15.3
(21.68)
At 10 minutes
27.1
(26.89)
23.6
(28.15)
19.0
(24.27)
At 15 minutes
33.5
(28.04)
27.2
(30.74)
21.6
(28.54)
At 30 minutes
39.7
(30.47)
33.9
(33.04)
23.1
(31.95)
At 45 minutes
41.6
(33.14)
33.3
(33.64)
19.9
(31.67)
At 1 hour
40.0
(34.64)
37.8
(37.21)
17.1
(30.67)
At 2 hours
35.3
(36.99)
33.2
(37.98)
10.1
(23.97)
At 3 hours
33.5
(37.06)
29.5
(37.09)
8.0
(22.07)
At 5 hours
28.8
(35.45)
31.0
(36.74)
8.0
(21.96)
At 6 hours
36.7
(34.78)
33.9
(32.54)
12.6
(24.10)
At 9 hours
49.5
(35.12)
39.4
(34.59)
17.5
(26.20)
At 12 hours
51.6
(33.42)
46.3
(34.44)
21.6
(27.46)
At 15 hours
55.7
(33.55)
45.9
(34.08)
21.4
(26.15)
At 18 hours
56.6
(33.00)
53.6
(33.98)
28.3
(30.07)
At 21 hours
63.6
(32.75)
63.2
(33.05)
27.4
(32.73)
At 24 hours
59.7
(33.73)
53.4
(34.87)
32.5
(35.25)
At 48 hours
69.4
(31.52)
60.8
(33.83)
38.2
(37.73)
At 72 hours
74.4
(31.01)
64.8
(35.41)
38.8
(38.77)
At 96 hours
74.6
(31.11)
67.0
(34.96)
39.4
(39.19)
At 120 hours
74.6
(31.15)
66.9
(34.89)
39.4
(39.19)
10. Secondary Outcome
Title Time From Administration of Study Drug to Administration of Rescue Medication
Description Time from administration of study drug to administration of rescue medication were censored at time of last pain assessment for participants who did not receive rescue medication. Rescue medication was additional pain medication, available to participants if they did not receive pain relief from the study drug. Rescue medication available during this study was IV morphine.
Time Frame Maximum up to 5 days

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized into the study and who received at least 1 dose of study medication. Missing data was imputed using worst observation carried forward (WOCF) recorded over prior six hours (including baseline, if appropriate) in this outcome measure.
Arm/Group Title Diclofenac (DIC075V) Ketorolac Placebo
Arm/Group Description Participants at high risk (weighing <50 k), age >= 65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received DIC075V 18.75 mg. Participants without any risk factor and weighing >95 kg received DIC075V 50 mg. Participants weighing >95 kg with any risk factor received DIC075V 18.75 mg. All other participants received DIC075V 37.5 mg. DIC075V was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants at high risk (weighing <50 k, >=65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received ketorolac tromethamine 15 mg. Participants without any risk factor and weighing >95 kg received ketorolac tromethamine 30 mg. Participants weighing >95 kg with any risk factor received ketorolac tromethamine 15 mg. All other participants received ketorolac tromethamine 30 mg. Ketorolac tromethamine was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants received saline as placebo as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration.
Measure Participants 145 60 72
Median (95% Confidence Interval) [Minutes]
220.0
137.0
51.0
11. Secondary Outcome
Title Cumulative Amount of Rescue Medication
Description In this outcome measure, cumulative amount of rescue medication used over 0-24, 0-48, 0-72, 0-96, and 0-120 hours were reported. Rescue medication was additional pain medication, available to participants if they did not receive pain relief from the study drug. Rescue medication available during this study was IV morphine.
Time Frame 0-24, 0-48, 0-72, 0-96 and 0-120 hours

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized into the study and who received at least 1 dose of study medication. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "number analyzed" signifies participants evaluable at specific rows. Missing data was imputed using WOCF recorded over prior six hours (including baseline, if appropriate) in this outcome measure.
Arm/Group Title Diclofenac (DIC075V) Ketorolac Placebo
Arm/Group Description Participants at high risk (weighing <50 k), age >= 65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received DIC075V 18.75 mg. Participants without any risk factor and weighing >95 kg received DIC075V 50 mg. Participants weighing >95 kg with any risk factor received DIC075V 18.75 mg. All other participants received DIC075V 37.5 mg. DIC075V was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants at high risk (weighing <50 k, >=65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received ketorolac tromethamine 15 mg. Participants without any risk factor and weighing >95 kg received ketorolac tromethamine 30 mg. Participants weighing >95 kg with any risk factor received ketorolac tromethamine 15 mg. All other participants received ketorolac tromethamine 30 mg. Ketorolac tromethamine was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants received saline as placebo as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration.
Measure Participants 107 44 68
0-24 hours
9.4
(7.20)
11.5
(7.81)
16.0
(10.61)
0-48 hours
11.1
(9.06)
15.5
(13.99)
19.0
(13.89)
0-72 hours
11.7
(9.56)
18.0
(20.11)
20.5
(16.19)
0-96 hours
11.8
(9.73)
18.1
(20.14)
20.5
(16.17)
0-120 hours
11.8
(9.73)
18.1
(20.17)
20.5
(16.17)
12. Secondary Outcome
Title Number of Participants According to Frequency of Use of Rescue Medication
Description In this outcome measure, number of participants are reported according to number of times they received rescue medication. Rescue medication was additional pain medication, available to participants if they did not receive pain relief from the study drug. Rescue medication available during this study was IV morphine. Only those categories with at least one nonzero value are reported.
Time Frame 0-24, 0-48, 0-72, 0-96 and 0-120 hours post first dose

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized into the study and who received at least 1 dose of study medication. Missing data was imputed using WOCF recorded over prior six hours (including baseline, if appropriate) in this outcome measure.
Arm/Group Title Diclofenac (DIC075V) Ketorolac Placebo
Arm/Group Description Participants at high risk (weighing <50 k), age >= 65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received DIC075V 18.75 mg. Participants without any risk factor and weighing >95 kg received DIC075V 50 mg. Participants weighing >95 kg with any risk factor received DIC075V 18.75 mg. All other participants received DIC075V 37.5 mg. DIC075V was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants at high risk (weighing <50 k, >=65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received ketorolac tromethamine 15 mg. Participants without any risk factor and weighing >95 kg received ketorolac tromethamine 30 mg. Participants weighing >95 kg with any risk factor received ketorolac tromethamine 15 mg. All other participants received ketorolac tromethamine 30 mg. Ketorolac tromethamine was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants received saline as placebo as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration.
Measure Participants 145 60 72
0 - 24 Hours: 0
39
26.9%
17
28.3%
4
5.6%
0 - 24 Hours: 1
26
17.9%
6
10%
7
9.7%
0 - 24 Hours: 2
26
17.9%
9
15%
6
8.3%
0 - 24 Hours: 3
19
13.1%
8
13.3%
11
15.3%
0 - 24 Hours: 4
8
5.5%
4
6.7%
9
12.5%
0 - 24 Hours: 5
9
6.2%
3
5%
9
12.5%
0 - 24 Hours: 6
7
4.8%
3
5%
3
4.2%
0 - 24 Hours: 7
3
2.1%
5
8.3%
7
9.7%
0 - 24 Hours: 8
2
1.4%
2
3.3%
4
5.6%
0 - 24 Hours: 9
3
2.1%
1
1.7%
4
5.6%
0 - 24 Hours: 11
1
0.7%
1
1.7%
3
4.2%
0 - 24 Hours: 12
1
0.7%
1
1.7%
2
2.8%
0 - 24 Hours: 13
1
0.7%
0
0%
1
1.4%
0 - 24 Hours: 14
0
0%
0
0%
1
1.4%
0 - 24 Hours: 15
0
0%
0
0%
1
1.4%
0-48 hours: 0
38
26.2%
16
26.7%
14
19.4%
0-48 hours: 1
23
15.9%
5
8.3%
7
9.7%
0-48 hours: 2
24
16.6%
10
16.7%
6
8.3%
0-48 hours: 3
14
9.7%
5
8.3%
10
13.9%
0-48 hours: 4
11
7.6%
2
3.3%
3
4.2%
0-48 hours: 5
7
4.8%
3
5%
8
11.1%
0-48 hours: 6
8
5.5%
2
3.3%
5
6.9%
0-48 hours: 7
6
4.1%
4
6.7%
8
11.1%
0-48 hours: 8
3
2.1%
3
5%
3
4.2%
0-48 hours: 9
4
2.8%
4
6.7%
5
6.9%
0-48 hours: 10
2
1.4%
2
3.3%
0
0%
0-48 hours: 11
3
2.1%
1
1.7%
5
6.9%
0-48 hours: 12
1
0.7%
2
3.3%
3
4.2%
0-48 hours: 13
1
0.7%
1
1.7%
1
1.4%
0-48 hours: 14
0
0%
0
0%
1
1.4%
0-48 hours: 15
0
0%
0
0%
1
1.4%
0-48 hours: 17
0
0%
0
0%
1
1.4%
0-48 hours: 20
0
0%
0
0%
1
1.4%
0-72 hours: 0
38
26.2%
16
26.7%
4
5.6%
0-72 hours: 1
23
15.9%
5
8.3%
7
9.7%
0-72 hours: 2
22
15.2%
10
16.7%
6
8.3%
0-72 hours: 3
15
10.3%
5
8.3%
10
13.9%
0-72 hours: 4
11
7.6%
2
3.3%
3
4.2%
0-72 hours: 5
6
4.1%
2
3.3%
5
6.9%
0-72 hours: 6
8
5.5%
2
3.3%
7
9.7%
0-72 hours: 7
4
2.8%
4
6.7%
6
8.3%
0-72 hours: 8
4
2.8%
2
3.3%
2
2.8%
0-72 hours: 9
3
2.1%
1
1.7%
9
12.5%
0-72 hours: 10
5
3.4%
4
6.7%
9
12.5%
0-72 hours: 11
3
2.1%
2
3.3%
0
0%
0-72 hours: 12
2
1.4%
1
1.7%
2
2.8%
0-72 hours: 13
1
0.7%
1
1.7%
3
4.2%
0-72 hours: 14
0
0%
0
0%
1
1.4%
0-72 hours: 15
0
0%
2
3.3%
2
2.8%
0-72 hours: 17
0
0%
1
1.7%
0
0%
0-72 hours: 19
0
0%
0
0%
1
1.4%
0-72 hours: 20
0
0%
0
0%
1
1.4%
0-72 hours: 21
0
0%
0
0%
1
1.4%
0-96 hours: 0
38
26.2%
16
26.7%
4
5.6%
0-96 hours: 1
23
15.9%
5
8.3%
7
9.7%
0-96 hours: 2
22
15.2%
10
16.7%
6
8.3%
0-96 hours: 3
15
10.3%
5
8.3%
10
13.9%
0-96 hours: 4
11
7.6%
2
3.3%
3
4.2%
0-96 hours: 5
6
4.1%
2
3.3%
5
6.9%
0-96 hours: 6
7
4.8%
2
3.3%
6
8.3%
0-96 hours: 7
5
3.4%
4
6.7%
7
9.7%
0-96 hours: 8
3
2.1%
2
3.3%
2
2.8%
0-96 hours: 9
3
2.1%
1
1.7%
9
12.5%
0-96 hours: 10
5
3.4%
3
5%
0
0%
0-96 hours: 11
3
2.1%
3
5%
2
2.8%
0-96 hours: 12
3
2.1%
1
1.7%
3
4.2%
0-96 hours: 13
1
0.7%
1
1.7%
1
1.4%
0-96 hours: 14
0
0%
0
0%
2
2.8%
0-96 hours: 15
0
0%
2
3.3%
2
2.8%
0-96 hours: 17
0
0%
1
1.7%
0
0%
0-96 hours: 19
0
0%
0
0%
1
1.4%
0-96 hours: 20
0
0%
0
0%
1
1.4%
0-96 hours: 21
0
0%
0
0%
1
1.4%
0-120 hours: 0
38
26.2%
16
26.7%
4
5.6%
0-120 hours: 1
23
15.9%
5
8.3%
7
9.7%
0-120 hours: 2
22
15.2%
10
16.7%
6
8.3%
0-120 hours: 3
15
10.3%
5
8.3%
10
13.9%
0-120 hours: 4
11
7.6%
2
3.3%
3
4.2%
0-120 hours: 5
6
4.1%
2
3.3%
5
6.9%
0-120 hours: 6
7
4.8%
2
3.3%
6
8.3%
0-120 hours: 7
5
3.4%
4
6.7%
7
9.7%
0-120 hours: 8
3
2.1%
2
3.3%
2
2.8%
0-120 hours: 9
3
2.1%
1
1.7%
9
12.5%
0-120 hours: 10
5
3.4%
3
5%
0
0%
0-120 hours: 11
3
2.1%
2
3.3%
2
2.8%
0-120 hours: 12
3
2.1%
2
3.3%
3
4.2%
0-120 hours: 13
1
0.7%
1
1.7%
1
1.4%
0-120 hours: 14
0
0%
0
0%
2
2.8%
0-120 hours: 15
0
0%
2
3.3%
2
2.8%
0-120 hours: 17
0
0%
1
1.7%
0
0%
0-120 hours: 19
0
0%
0
0%
1
1.4%
0-120 hours: 20
0
0%
0
0%
1
1.4%
0-120 hours: 21
0
0%
0
0%
1
1.4%
13. Secondary Outcome
Title Participant Global Evaluation Over Time
Description Participants global evaluation of study medication was accessed on a scale ranging from scale 0 to 4 where 0= poor, 1= fair, 2= good, 3= very good, 4= excellent where higher score represented better outcome.
Time Frame 0-24, 0-48, 0-120 hours post-dose

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized into the study and who received at least 1 dose of study medication. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "number analyzed" signifies participants evaluable at specific rows.
Arm/Group Title Diclofenac (DIC075V) Ketorolac Placebo
Arm/Group Description Participants at high risk (weighing <50 k), age >= 65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received DIC075V 18.75 mg. Participants without any risk factor and weighing >95 kg received DIC075V 50 mg. Participants weighing >95 kg with any risk factor received DIC075V 18.75 mg. All other participants received DIC075V 37.5 mg. DIC075V was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants at high risk (weighing <50 k, >=65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received ketorolac tromethamine 15 mg. Participants without any risk factor and weighing >95 kg received ketorolac tromethamine 30 mg. Participants weighing >95 kg with any risk factor received ketorolac tromethamine 15 mg. All other participants received ketorolac tromethamine 30 mg. Ketorolac tromethamine was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants received saline as placebo as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration.
Measure Participants 141 59 70
0-24 Hours
2.6
(1.27)
2.4
(1.16)
1.1
(1.25)
0-48 Hours
2.9
(1.15)
2.6
(0.86)
1.9
(1.42)
0-120 Hours
2.9
(1.26)
2.6
(1.16)
1.3
(1.38)
14. Secondary Outcome
Title Time to Perceptible Relief
Description Participants were instructed to stop the first stopwatch at the onset of perceptible pain relief after first dose. Event times of participants not reporting perceptible relief were censored at 6 hours; event times of participants who withdrew or were administered rescue medication were censored at time of withdrawal or rescue. Kaplan-Meier estimate was used for analysis.
Time Frame Within 6 hours of first dose on Day 1

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized into the study and who received at least 1 dose of study medication.
Arm/Group Title Diclofenac (DIC075V) Ketorolac Placebo
Arm/Group Description Participants at high risk (weighing <50 k), age >= 65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received DIC075V 18.75 mg. Participants without any risk factor and weighing >95 kg received DIC075V 50 mg. Participants weighing >95 kg with any risk factor received DIC075V 18.75 mg. All other participants received DIC075V 37.5 mg. DIC075V was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants at high risk (weighing <50 k, >=65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received ketorolac tromethamine 15 mg. Participants without any risk factor and weighing >95 kg received ketorolac tromethamine 30 mg. Participants weighing >95 kg with any risk factor received ketorolac tromethamine 15 mg. All other participants received ketorolac tromethamine 30 mg. Ketorolac tromethamine was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants received saline as placebo as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration.
Measure Participants 145 60 72
Median (Full Range) [Minutes]
10.0
14.4
15.0
15. Secondary Outcome
Title Time to Meaningful Relief
Description Participants were instructed to stop the second stopwatch at the onset of meaningful pain relief after first dose. Event times of participants not reporting meaningful relief were censored at 6 hours; event times of participants who withdrew or were administered rescue medication were censored at time of withdrawal or rescue. Kaplan-Meier estimate was used for analysis.
Time Frame Within 6 hours of first dose on Day 1

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized into the study and who received at least 1 dose of study medication.
Arm/Group Title Diclofenac (DIC075V) Ketorolac Placebo
Arm/Group Description Participants at high risk (weighing <50 k), age >= 65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received DIC075V 18.75 mg. Participants without any risk factor and weighing >95 kg received DIC075V 50 mg. Participants weighing >95 kg with any risk factor received DIC075V 18.75 mg. All other participants received DIC075V 37.5 mg. DIC075V was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants at high risk (weighing <50 k, >=65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received ketorolac tromethamine 15 mg. Participants without any risk factor and weighing >95 kg received ketorolac tromethamine 30 mg. Participants weighing >95 kg with any risk factor received ketorolac tromethamine 15 mg. All other participants received ketorolac tromethamine 30 mg. Ketorolac tromethamine was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants received saline as placebo as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration.
Measure Participants 145 60 72
Median (95% Confidence Interval) [Minutes]
41.6
42.5
NA

Adverse Events

Time Frame
Adverse Event Reporting Description Same event may appear as both an adverse events (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Arm/Group Title Diclofenac (DIC075V) Ketorolac Placebo
Arm/Group Description Participants at high risk (weighing <50 k), age >= 65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received DIC075V 18.75 mg. Participants without any risk factor and weighing >95 kg received DIC075V 50 mg. Participants weighing >95 kg with any risk factor received DIC075V 18.75 mg. All other participants received DIC075V 37.5 mg. DIC075V was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants at high risk (weighing <50 k, >=65 years, elevated NSAID-related GI risk factors, or with hepatic or renal impairment) received ketorolac tromethamine 15 mg. Participants without any risk factor and weighing >95 kg received ketorolac tromethamine 30 mg. Participants weighing >95 kg with any risk factor received ketorolac tromethamine 15 mg. All other participants received ketorolac tromethamine 30 mg. Ketorolac tromethamine was administered as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration. Participants received saline as placebo as IV bolus every 6 hours for up to 5 days. Participants returned to the clinic for a safety follow-up 5-9 days after discharge and had a safety follow-up telephone call 30-37 days after the last study drug administration.
All Cause Mortality
Diclofenac (DIC075V) Ketorolac Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN) / (NaN)
Serious Adverse Events
Diclofenac (DIC075V) Ketorolac Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 7/145 (4.8%) 4/60 (6.7%) 3/72 (4.2%)
Cardiac disorders
Cardiac failure congestive 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Eye disorders
Blindness unilateral 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Gastrointestinal disorders
Abdominal pain 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Infections and infestations
Clostridium difficile colitis 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Staphylococcal infection 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Urinary tract infection 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Injury, poisoning and procedural complications
Femur fracture 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Seroma 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Musculoskeletal and connective tissue disorders
Chondrocalcinosis pyrophosphate 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Renal and urinary disorders
Renal failure acute 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Vascular disorders
Deep vein thrombosis 3/145 (2.1%) 0/60 (0%) 0/72 (0%)
Hypotension 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Other (Not Including Serious) Adverse Events
Diclofenac (DIC075V) Ketorolac Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 109/145 (75.2%) 46/60 (76.7%) 60/72 (83.3%)
Blood and lymphatic system disorders
Anaemia 9/145 (6.2%) 7/60 (11.7%) 8/72 (11.1%)
Haemorrhagic anaemia 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Lymphadenopathy 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Thrombocytopenia 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Cardiac disorders
Angina pectoris 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Atrial fibrillation 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Bradycardia 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Tachycardia 1/145 (0.7%) 1/60 (1.7%) 1/72 (1.4%)
Ear and labyrinth disorders
Ear disorder 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Tinnitus 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Eye disorders
Eye oedema 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Gastrointestinal disorders
Abdominal distension 1/145 (0.7%) 0/60 (0%) 1/72 (1.4%)
Abdominal hernia 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Abdominal pain 3/145 (2.1%) 0/60 (0%) 0/72 (0%)
Constipation 19/145 (13.1%) 6/60 (10%) 11/72 (15.3%)
Diarrhoea 7/145 (4.8%) 0/60 (0%) 1/72 (1.4%)
Dry mouth 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Dyspepsia 3/145 (2.1%) 2/60 (3.3%) 1/72 (1.4%)
Faeces discoloured 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Flatulence 4/145 (2.8%) 1/60 (1.7%) 2/72 (2.8%)
Haematemesis 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Nausea 36/145 (24.8%) 18/60 (30%) 26/72 (36.1%)
Rectal haemorrhage 1/145 (0.7%) 1/60 (1.7%) 0/72 (0%)
Vomiting 11/145 (7.6%) 6/60 (10%) 14/72 (19.4%)
General disorders
Adverse drug reaction 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Application site inflammation 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Application site reaction 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Application site vesicles 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Asthenia 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Chills 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Discomfort 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Fatigue 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Feeling drunk 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Feeling hot 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Infusion site erythema 0/145 (0%) 0/60 (0%) 2/72 (2.8%)
Infusion site pain 11/145 (7.6%) 5/60 (8.3%) 5/72 (6.9%)
Infusion site pruritus 2/145 (1.4%) 0/60 (0%) 0/72 (0%)
Infusion site reaction 1/145 (0.7%) 0/60 (0%) 1/72 (1.4%)
Infusion site swelling 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Injection site pain 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Non-cardiac chest pain 2/145 (1.4%) 0/60 (0%) 1/72 (1.4%)
Oedema peripheral 8/145 (5.5%) 3/60 (5%) 2/72 (2.8%)
Pain 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Pyrexia 4/145 (2.8%) 3/60 (5%) 9/72 (12.5%)
Tenderness 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Infections and infestations
Bronchitis 1/145 (0.7%) 0/60 (0%) 1/72 (1.4%)
Cellulitis 2/145 (1.4%) 1/60 (1.7%) 0/72 (0%)
Gastroenteritis viral 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Localised infection 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Nasopharyngitis 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Pneumonia 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Postoperative wound infection 8/145 (5.5%) 1/60 (1.7%) 2/72 (2.8%)
Sinusitis 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Tooth infection 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Urinary tract infection 3/145 (2.1%) 1/60 (1.7%) 0/72 (0%)
Viral pharyngitis 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Injury, poisoning and procedural complications
Anaemia postoperative 7/145 (4.8%) 2/60 (3.3%) 3/72 (4.2%)
Contusion 1/145 (0.7%) 2/60 (3.3%) 1/72 (1.4%)
Incision site complication 2/145 (1.4%) 1/60 (1.7%) 0/72 (0%)
Post procedural complication 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Post procedural oedema 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Post procedural swelling 2/145 (1.4%) 0/60 (0%) 0/72 (0%)
Postoperative ileus 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Postoperative wound complication 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Procedural hypertension 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Procedural pain 2/145 (1.4%) 0/60 (0%) 0/72 (0%)
Procedural site reaction 8/145 (5.5%) 3/60 (5%) 0/72 (0%)
Seroma 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Wound dehiscence 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Wound secretion 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Investigations
Alanine aminotransferase increased 4/145 (2.8%) 1/60 (1.7%) 3/72 (4.2%)
Aspartate aminotransferase increased 4/145 (2.8%) 1/60 (1.7%) 3/72 (4.2%)
Blood alkaline phosphatase increased 0/145 (0%) 1/60 (1.7%) 3/72 (4.2%)
Blood amylase increased 2/145 (1.4%) 1/60 (1.7%) 0/72 (0%)
Blood bilirubin increased 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Blood creatine phosphokinase increased 21/145 (14.5%) 8/60 (13.3%) 9/72 (12.5%)
Blood glucose increased 1/145 (0.7%) 0/60 (0%) 1/72 (1.4%)
Blood lactate dehydrogenase increased 1/145 (0.7%) 0/60 (0%) 1/72 (1.4%)
Body temperature increased 2/145 (1.4%) 2/60 (3.3%) 5/72 (6.9%)
Gamma-glutamyltransferase increased 0/145 (0%) 1/60 (1.7%) 3/72 (4.2%)
Haematocrit decreased 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Lipase increased 1/145 (0.7%) 1/60 (1.7%) 0/72 (0%)
Neutrophil count increased 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Platelet count increased 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Weight decreased 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Metabolism and nutrition disorders
Decreased appetite 1/145 (0.7%) 0/60 (0%) 2/72 (2.8%)
Dehydration 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Hypocalcaemia 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Hypokalaemia 1/145 (0.7%) 1/60 (1.7%) 4/72 (5.6%)
Metabolic acidosis 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Musculoskeletal and connective tissue disorders
Back pain 3/145 (2.1%) 2/60 (3.3%) 0/72 (0%)
Bursitis 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Chondrocalcinosis pyrophosphate 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Haemarthrosis 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Joint swelling 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Limb discomfort 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Muscle spasms 3/145 (2.1%) 0/60 (0%) 1/72 (1.4%)
Musculoskeletal pain 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Myalgia 1/145 (0.7%) 1/60 (1.7%) 0/72 (0%)
Rhabdomyolysis 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Sensation of heaviness 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Nervous system disorders
Amnesia 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Burning sensation 2/145 (1.4%) 0/60 (0%) 0/72 (0%)
Cognitive disorder 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Confusional state 1/145 (0.7%) 0/60 (0%) 2/72 (2.8%)
Disorientation 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Dizziness 16/145 (11%) 5/60 (8.3%) 5/72 (6.9%)
Dizziness postural 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Dysgeusia 2/145 (1.4%) 1/60 (1.7%) 1/72 (1.4%)
Head discomfort 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Headache 12/145 (8.3%) 5/60 (8.3%) 5/72 (6.9%)
Hypoaesthesia 2/145 (1.4%) 0/60 (0%) 0/72 (0%)
Lethargy 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Paraesthesia 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Sciatica 1/145 (0.7%) 0/60 (0%) 1/72 (1.4%)
Sinus headache 2/145 (1.4%) 0/60 (0%) 0/72 (0%)
Somnolence 2/145 (1.4%) 0/60 (0%) 1/72 (1.4%)
Syncope 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Syncope vasovagal 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Tension headache 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Psychiatric disorders
Abnormal dreams 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Anxiety 1/145 (0.7%) 1/60 (1.7%) 1/72 (1.4%)
Depression 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Hallucination 0/145 (0%) 2/60 (3.3%) 1/72 (1.4%)
Insomnia 7/145 (4.8%) 4/60 (6.7%) 5/72 (6.9%)
Nightmare 1/145 (0.7%) 0/60 (0%) 1/72 (1.4%)
Restlessness 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Renal and urinary disorders
Dysuria 1/145 (0.7%) 1/60 (1.7%) 0/72 (0%)
Haematuria 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Nephrolithiasis 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Renal failure acute 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Renal tubular necrosis 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Urinary retention 3/145 (2.1%) 0/60 (0%) 0/72 (0%)
Reproductive system and breast disorders
Priapism 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Respiratory, thoracic and mediastinal disorders
Cough 1/145 (0.7%) 0/60 (0%) 1/72 (1.4%)
Dry throat 1/145 (0.7%) 0/60 (0%) 1/72 (1.4%)
Dyspnoea 1/145 (0.7%) 1/60 (1.7%) 0/72 (0%)
Epistaxis 2/145 (1.4%) 0/60 (0%) 0/72 (0%)
Haemoptysis 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Hiccups 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Pharyngolaryngeal pain 3/145 (2.1%) 0/60 (0%) 1/72 (1.4%)
Pulmonary congestion 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Skin and subcutaneous tissue disorders
Blister 0/145 (0%) 1/60 (1.7%) 2/72 (2.8%)
Cold sweat 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Dermatitis allergic 1/145 (0.7%) 0/60 (0%) 1/72 (1.4%)
Erythema 2/145 (1.4%) 1/60 (1.7%) 3/72 (4.2%)
Night sweats 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Petechiae 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Pruritus 5/145 (3.4%) 5/60 (8.3%) 5/72 (6.9%)
Pruritus generalised 1/145 (0.7%) 1/60 (1.7%) 2/72 (2.8%)
Rash 4/145 (2.8%) 6/60 (10%) 0/72 (0%)
Rash erythematous 0/145 (0%) 0/60 (0%) 1/72 (1.4%)
Rash generalised 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Rash maculovesicular 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Rash pruritic 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Urticaria 2/145 (1.4%) 1/60 (1.7%) 0/72 (0%)
Hyperhidrosis 1/145 (0.7%) 0/60 (0%) 1/72 (1.4%)
Surgical and medical procedures
Post procedural drainage 0/145 (0%) 1/60 (1.7%) 0/72 (0%)
Vascular disorders
Flushing 2/145 (1.4%) 1/60 (1.7%) 0/72 (0%)
Hot flush 1/145 (0.7%) 0/60 (0%) 0/72 (0%)
Hypertension 0/145 (0%) 0/60 (0%) 2/72 (2.8%)
Hypotension 6/145 (4.1%) 1/60 (1.7%) 2/72 (2.8%)
Orthostatic hypotension 1/145 (0.7%) 0/60 (0%) 0/72 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Results Point of Contact

Name/Title Pfizer ClinicalTrials.gov Call Center
Organization Pfizer Inc.
Phone 1-800-718-1021
Email ClinicalTrials.gov_Inquiries@pfizer.com
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00507026
Other Study ID Numbers:
  • DFC-005
  • C1211009
First Posted:
Jul 25, 2007
Last Update Posted:
Oct 29, 2021
Last Verified:
Sep 1, 2021