An Open-Label Safety Study Of DIC075V (Intravenous Diclofenac Sodium) In Patients With Acute Post-Operative Pain

Study Overview
=================
Brief Summary
-----------------
This is an open-label, multiple-dose, safety study of DIC075V in patients with acute post-operative pain following abdominal or orthopedic surgery.

Detailed Description
-----------------
This is an open-label, multiple-dose, multiple-day, single-arm safety study of repeat-doses of DIC075V in patients with acute post-operative pain following abdominal (i.e., non-laparoscopic abdominal surgeries) or orthopedic (e.g., hip or knee joint replacement) surgery. Eligible patients will receive DIC075V IV bolus q6 hours. Safety assessments will be collected at baseline (immediately prior to starting DIC075V therapy) and at study discharge or early termination.

Official Title
-----------------
An Open-Label, Multiple-Dose, Multiple-Day, Non-Randomized, Single-Arm Safety Study Of Repeat-Doses Of DIC075V (Intravenous Diclofenac Sodium) In Patients With Acute Post-Operative Pain

Conditions
-----------------
Pain, Postoperative

Intervention / Treatment
-----------------
* Drug: DIC075V (intravenous diclofenac sodium)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: abdominal ( non-laparoscopic abdominal surgeries) or orthopedic ( hip or knee joint replacement) surgery or other surgeries requiring multiple doses of parenterally administered NSAIDs over multiple days Expected stay > 48 hrs Exclusion Criteria: bilirubin > 2.5 mg/dl prothrombin time is > 20% above the upper limit of normal serum creatinine is > 1.9 mg/dl at screening. known allergy or hypersensitivity to diclofenac, other NSAIDs,

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>IV administration of multiple doses of DIC075V (intravenous diclofenac sodium) over multiple days | Drug: DIC075V (intravenous diclofenac sodium)<br>* multiple doses up to 5 days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were events between first dose of study drug and up to 37 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs included SAEs and all non-SAEs that occurred during the study. | Day 1 of dosing up to maximum of 37 days after last dose (maximum up to 42 days) | 
| Number of Participants Who Took at Least 1 Concomitant Medication | Concomitant medications were medications that were taken concurrently on or after first dose of study drug. | Day 1 of dosing up to maximum of 37 days after last dose (maximum up to 42 days) | 
| Number of Participants With Abnormal Urinalysis Findings | Urine parameters included gravity, glucose, protein, and bilirubin. Abnormalities were judged by the investigator. | Baseline (Day 1, immediately before dosing) up to study discharge/early termination (maximum up to Day 5) | 
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities at Baseline | 12-lead ECG parameters were evaluated. Clinically significant abnormal ECG findings were based on investigator's discretion. | Baseline (Day 1, immediately before dosing) | 
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities at Study Discharge/Early Termination | 12-lead ECG parameters were evaluated. Clinically significant abnormal ECG findings were based on investigator's discretion. | Study discharge/early termination (maximum up to Day 5) | 
| Change From Baseline in Blood Pressure at Study Discharge/Early Termination | Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) in millimeter of mercury (mmHg) was reported. The blood pressure was assessed after the participant had taken rest for 5 minutes. | Baseline (Day 1, immediately before dosing), Study discharge/early termination (maximum up to 5 days) | 
| Change From Baseline in Blood Pressure at Clinic Follow-up Visit | Change from baseline in SBP and DBP in mmHg was reported. The blood pressure was assessed after the participant had taken rest for 5 minutes. | Baseline (Day 1, immediately before dosing), Clinic follow-up visit (4-10 days after last dose, maximum up to 15 days) | 
| Change From Baseline in Respiratory Rate at Study Discharge/Early Termination | Respiratory rate was measured after the participant had taken rest for 5 minutes. | Baseline (Day 1, immediately before dosing), Study discharge/early termination (maximum up to 5 days) | 
| Change From Baseline in Respiratory Rate at Clinic Follow-up Visit | Respiratory rate was measured after the participant had taken rest for 5 minutes. | Baseline (Day 1, immediately before dosing), Clinic follow-up visit (4-10 days after last dose, maximum up to 15 days) | 
| Change From Baseline in Heart Rate at Study Discharge/Early Termination | Change from baseline in heart rate in beats per minute was reported. The heart rate was assessed after the participant had taken rest for 5 minutes. | Baseline (Day 1, immediately before dosing), Study discharge/early termination (maximum up to 5 days) | 
| Change From Baseline in Heart Rate at Clinic Follow-up Visit | Change from baseline in heart rate in beats per minute was reported. The heart rate was assessed after the participant had taken rest for 5 minutes. | Baseline (Day 1, immediately before dosing), Clinic follow-up visit (4-10 days after last dose, maximum up to 15 days) | 
| Number of Participants With Wound Assessment at Study Discharge/Early Termination | Wound assessment had 6 questions, completed by investigator/sub-investigator. Question related to extent of healing; extent and degree of inflammation and extent of drainage had options: much better than expected, better than expected, normal, slower than expected, and much slower than expected. Question related to separation of surgical incision had options: no separation, barely detectible separation, localized separation, mostly separated, and complete separation (dehiscence). Question related to infection at surgical site had options: definitely, no infection, possibly infected, probably infected, certainly infected, and abscess/gross cellulitis. Question related to prescription of postoperative systemic antibiotics had options: no, yes for prophylaxis, and yes for infection. Every question there was category Not Done for participants with no wound assessment other than the reason 'missing' and category Missing, where participants were missing for wound assessment. | Study discharge/early termination (maximum up to Day 5) | 
| Number of Participants With Thrombophlebitis Assessment Evaluation at Baseline | Thrombophlebitis assessment evaluation was done using following grades: 0 equals to (=) no reaction, 1= tenderness along the vein, 2= continuous tenderness of pain with redness, 3= palpable swelling or thrombosis within length of cannula, 4= palpable swelling or thrombosis beyond the length of the cannula and 5= palpable swelling or thrombosis beyond the length of the cannula with overt infection. | Baseline (Day 1, immediately before dosing) | 
| Number of Participants With Thrombophlebitis Assessment Evaluation at Study Discharge/Early Termination | Thrombophlebitis assessment evaluation was done using following grades: 0= no reaction, 1= tenderness along the vein, 2= continuous tenderness of pain with redness, 3= palpable swelling or thrombosis within length of cannula, 4= palpable swelling or thrombosis beyond the length of the cannula and 5= palpable swelling or thrombosis beyond the length of the cannula with overt infection. | Study discharge/early termination (maximum up to Day 5) | 
| Number of Participants With Clinically Significant Physical Examination Abnormalities at Screening | Physical examination included the assessment of general appearance, skin; head, ears, eyes, nose, and throat (HEENT); neck/thyroid; oral cavity; lymph nodes; cardiovascular; lungs; abdomen; genitourinary; neurologic and joints/extremities. Clinically significant physical examination findings were based on investigator's discretion. | Screening (0 to 21 days prior to surgery) | 
| Number of Participants With Clinically Significant Physical Examination Abnormalities at Clinic Follow-up Visit | Physical examination included the assessment of general appearance, skin; HEENT; neck/thyroid; oral cavity; lymph nodes; cardiovascular; lungs; abdomen; genitourinary; neurologic and joints/extremities. Clinically significant physical examination findings were based on investigator's discretion. | Clinic follow-up visit (4-10 days after last dose, maximum up to 15 days) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
safety, diclofenac, pain, postoperative