| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| To investigate the efficacy and safety of the CollaRx Bupivacaine Implant in women following abdominal hysterectomy or other nonlaparoscopic benign gynecological procedure |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10044080 |
| E.1.2 | Term | Total abdominal hysterectomy |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To compare the narcotic-sparing effect of the CollaRx Bupivacaine Implant
(bupivacaine sponge) with the placebo sponge for the treatment of pain in
the abdominal hysterectomy wound for the first 24 hours after surgery. |
|
| E.2.2 | Secondary objectives of the trial |
To compare the narcotic-sparing effect of the bupivacaine sponge with
the placebo sponge for the treatment of pain in the abdominal
hysterectomy wound over 48 and 72 hours after surgery.
To evaluate the analgesic effect of the bupivacaine sponge compared
with placebo sponge for the treatment of pain in the abdominal
hysterectomy wound.
To assess the safety and tolerability of the bupivacaine sponge when
implanted into abdominal hysterectomy wounds during open surgery. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
To be eligible for entry into the study, patients must meet all of the
following inclusion criteria prior to surgery:
1. Must be a woman who is at least 18 but not more than 75 years of age.
2. Have a body mass index (BMI) > 19 and < 40 kg/m2.
3. Had planned an elective total abdominal hysterectomy for reasons
other than malignancies (such as uterine adenocarcinoma, cervical
cancer or leiomyosarcoma) to be performed according to standard
surgical technique using a standard incision and under general
anesthesia with the following caveats:
a. Laparoscopic procedures or supraumbilical or Maylard incisions
will not be allowed.
b. A nonlaparoscopic incision for benign non-hysterectomy
gynecological procedures (such as myomectomy or adnexal
surgery) is acceptable if the surgical indication is not to treat pelvic
pain.
c. No concomitant vaginal procedures such as anterior and posterior
colporrhaphy (A&P repairs) are allowed. An abdominal
urethropexy and an incidental appendectomy will be allowed.
4. Have a risk classification of I, II or III according to the American
Society of Anesthesiologists (ASA) (see Appendix III).
5. Have a negative pregnancy test within 14 days of surgery, if patient is
of childbearing potential (< 55 years).
6. Be free of other physical or mental conditions which, in the opinion of
the Investigator, may confound quantification of postoperative pain
resulting from the abdominal hysterectomy.
7. Have the ability to read, understand and comply with the study
procedures and the use of the pain scales; be deemed capable of operating a patient-controlled analgesia (PCA) device; and be able to
communicate meaningfully with the study observer and staff.
8. Patient or the patient’s legal representative must voluntarily sign and
date an informed consent form (ICF), approved by an Institutional
Review Board (IRB), prior to the conduct of any study-specific
procedures.
9. Patient or the patient’s legal representative must be able to fluently
speak and understand English and be able to provide meaningful
written informed consent for the study. |
|
| E.4 | Principal exclusion criteria |
1. Known hypersensitivity to amide local anesthetics, opioids, bovine
products or to inactive ingredients of the test article.
2. Presence of clinically significant cardiac arrhythmias or
atrioventricular (AV) conduction disorders. Cardiac arrhythmias or
atrioventricular (AV) conduction disorders that are abnormal, but the
investigator considers them not to be clinically significant with respect
to the study, require prior medical monitor approval.
3. Concomitant use of other amide local anesthetics.
4. Concomitant use of antiarrhythmics (eg, amiodarone).
5. Concomitant use of propranolol.
6. Concomitant use of strong/moderate CYP3A4 inhibitors or inducers
(eg, macrolide antibiotics and grapefruit juice).
7. Has used aspirin or aspirin-containing products within 7 days of
surgery. Aspirin at a dose of Q 325 mg is allowed for cardiovascular
prophylaxis if the subject has been on a stable dose regimen
for R 30 days prior to Screening.
8. Previous major surgery in the last 3 months.
9. Requires any additional surgical procedures either related or unrelated
to the abdominal hysterectomy during the same hospitalization (except
for the specific allowed procedures noted in above Inclusion Criteria).
10. Received neuraxial (spinal or epidural) opioid analgesics either prior to
or during the abdominal hysterectomy.
11. Received local anesthetic infiltration of the surgical wound prior to,
during or immediately after closure.
12. Is scheduled to receive postoperative local anesthetics via an
indwelling catheter (either neuraxial or regional).
13. Patient underwent additional procedures during surgery, such as lysis
of many adhesions, which in the opinion of the Investigator increased
the visceral pain.
14. Has known or suspected history of alcohol or drug abuse or misuse
within the previous 3 years or evidence for tolerance or physical
dependency on opioids analgesics or sedative-hypnotic medications.
15. Uses opioids or tramadol daily for > 7 days prior to test article
administration. Patients who, in the Investigator’s opinion, are
developing opioid tolerance are to be excluded.
16. Has impaired liver function, aspartate aminotransferase (AST)/alanine
transaminase (ALT)/bilirubin R 3.0 times the upper limit of normal
(ULN), active hepatic disease, evidence of clinically significant liver disease or other condition (eg, alcoholism, cirrhosis or hepatitis) that
may suggest the potential for an increased susceptibility to hepatic
toxicity with exposure to test article.
17. Presence of any clinically significant unstable cardiac, neurological,
immunological, renal or hematological disease or any other condition
that in the opinion of the Investigator could compromise the patient’s
welfare, ability to communicate with the study staff or otherwise
contraindicate study participation.
18. Patient is judged by the investigator to be at risk for infection or slow
wound healing.
19. Patient has a chronic painful condition that might confound the
assessment of pain associated with the abdominal hysterectomy.
20. Has taken pain medication (including nonsteroidal anti-inflammatory
drugs [NSAIDs]) that, in the opinion of the Investigator, would be
expected to confound the analgesic responses the day of surgery.
21. Has been treated within 2 weeks of surgery with agents that could
affect the analgesic response (such as central alpha agents [clonidine
and tizanidine], neuroleptic agents and other anti-psychotic agents).
22. Has been treated with monoamine oxidase inhibitors (MAOIs) or
whose treatment with these has been stopped fewer than 10 days prior
to surgery.
23. Has been treated with corticosteroids or whose treatment with these has
been stopped < 7 days prior surgery (inhaled corticosteroids are
acceptable).
24. History of participation in a clinical trial (investigational or marketed
product) in the previous 30 days.
25. Has been hemodynamically unstable at any point in the previous
4 weeks or becomes hemodynamically unstable during surgery.
26. Required blood transfusion in the previous month, except as related to
uterine bleeding caused by uterine fibroids.
27. Has hemoglobin levels < 10 g/dL or < 8 g/dL for patients with an
anemia secondary to heavy uterine bleeding caused by uterine fibroids.
28. Has platelet count < 100,000/mm.
29. Is considered by the Investigator to be unreliable or incapable of
complying with the requirements of the protocol. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Efficacy parameters of bupivacaine
• Total use of opioid rescue analgesia over 0 to 24 hours
• Total use of opioid rescue analgesia over 0 to 48 hours
• Total use of opioid rescue analgesia over 0 to 72 hours
• Pain intensity rating on the VAS
• Pain intensity rating on a 4-point Likert scale
• Time to first use of opioid rescue analgesia
Safety parameters
• Treatment-emergent AEs
• Vital signs - heart rate, respiration rate, systolic and diastolic blood
pressure and body temperature |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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