A phase Ib study to investigate the safety and pharmacokinetics of BR-003 in patients undergoing spinal fusion surgery

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 6

Inclusion Criteria

In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
1. Males and females aged between 18 years and 80 years (inclusive)
2. Planned for open or percutaneous posterior spinal stabilisation with 4 (for
cohort I) or 6 (for
cohort II) pedicle screws with a diameter of 5 to 7.5 mm (inclusive) with or
without concomitant
posterolateral fusion, vertebral augmentation, intervertebral body fusion
devices, osteotomies,
and posterior decompression. Only primary instrumented spinal surgery cases can
be included.
3. Willing and able to comply with the protocol for the duration of the study
4. Give written informed consent prior to any study-related procedure not part
of the standard
practice, with the understanding that the consent may be withdrawn by the
subject at any time
without prejudice to his/her (post-)surgery care
5. Females are eligible only if not currently pregnant, nursing, or planning to
become pregnant
during the study or within 9 months after study drug administration. Female
subjects must be surgically sterile, at least 2 years menopausal, or using an
acceptable method of birth control.
WOCBP, must have a documented negative pregnancy test within 24 hours before
surgery.

Exclusion Criteria

1. Concomitant anterior/lateral procedures (e.g. anteriorly placed vertebral
cage, anterior plating,
ALIF/XLIF)
2. Use of ilium screws or use of (additional) pedicle screws, with a size <
5 mm or > 7.5 mm.
3. Indication for surgery being:
a. Active or previous (para)spinal infection
b. Metastatic, malignant or benign tumours of the spine
c. Fracture/other traumatic injury
4. Known high risk of intra-/postoperative surgical complications (e.g.
patients having previously
undergone more than 2 non-instrumented spinal surgeries at the index level)
5. Planned use of a surgical drain
6. Planned use of an epidural catheter
7. Use of local amino-amide or amino-ester anaesthetics within 5 days prior to
the scheduled
surgery (10 days in case of slow release products), peri-op and post op for the
first two weeks after the surgery.
8. Has a pre-existing concurrent acute or chronic painful physical/restrictive
condition expected to
require analgesic treatment in the postoperative period for pain that is not
strictly related to the
surgical indication and which may confound the postoperative assessments.
9. Has a medical condition such that, in the opinion of the Investigator,
participating in the study
would pose a health risk to the subject or confound the postoperative
assessments. Conditions
may include, but are not limited to, the following:
a. History of allergic reactions to bupivacaine or excipients or BR-003, or if
the
investigational product is otherwise contra-indicated
b. ASA-classification >3, as assessed during the most recent pre-operative
screening.
c. Clinically significant renal or hepatic abnormalities (defined as an AST or
ALT > 3x
Upper limit of normal (ULN), creatinine > 2x ULN)
d. History of clinically significant cardiac abnormality such as myocardial
infarction within
6 months prior to study participation, NYHA class III or IV, or clinically
significant
abnormalities on ECG
e. History of coronary artery bypass graft surgery within 12 months prior to
study
participation
10. Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in
the opinion of the
Investigator, could interfere with study assessments or compliance
11. A body mass index (BMI) > 39 kg/m2 or patients with a weight below 50 kg
12. History of, suspected, or known addiction to or abuse of illicit drug(s),
prescription medicine(s),
or alcohol
13. As per subject history and/or medical records, has active infection or is
currently undergoing
treatment for Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV)
14. Participation in another interventional study

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary objective:<br /><br>- Assess systemic safety by confirming that the Cmax of BR-003 when<br /><br>co-implanted with a pedicle screw onto the spine, stays below the known toxic<br /><br>levels of 2000ng/mL</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary objectives:<br /><br>- To investigate additional pharmacokinetic parameters (Tmax, AUC, T1/2)<br /><br>- Assess the safety of BR-003<br /><br>• Incidence, classification and grading of Adverse Events<br /><br>• Clinical laboratory results (blood chemistry)<br /><br>• ECG data<br /><br>• Wound healing<br /><br>• Vital signs, neurological assessment<br /><br>• Radiological assessment</p><br>