Moderate to severe acute post-operative pain in subjects following primary unilateral first metatarsal bunionectomy MedDRA version: 14.1 Level: SOC Classification code 10028395 Term: Musculoskeletal and connective tissue disorders System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: Xen2174
Product Code: Xen2174
Pharmaceutical Form: Powder for solution for injection
Current Sponsor code: Xen2174
Concentration unit: mg milligram(s)
Concentration type: equal
Concentra
Sponsors
Xenome Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Subject is able to read and voluntarily sign the written informed consent document as approved by the Competent Authority, if applicable, and Independent Ethics Committee (IEC), and is given the opportunity to ask questions regarding the study prior to signing the informed consent and performance of any study-specific procedures. • Subject must require primary unilateral first metatarsal bunionectomy surgery (including osteotomy) to correct hallux valgus • Subject must be male or female 18-65 years of age. • Subject is Class ASA 1 or ASA 2 using the American Society of Anesthesiologists Physical Status Classification System. • If female, subject is non-lactating, and is either: 1. not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy; or 2. of childbearing potential but is not pregnant as confirmed by negative serum pregnancy test at the time of screening, and is practicing one of the following methods of birth control: oral, transdermal or parenteral contraceptives for 3 months prior to Study Drug administration or double-barrier method. If serum pregnancy test results are inconclusive, then the pre-surgical urine pregnancy test will determine eligibility. • Subject must be willing and able to comply with the protocol, and able to score their pain intensity. • Subject is in good health as determined by the Investigator on the basis of medical history, physical examination, ECG, and screening laboratory results. • Subject must be suitable for intrathecal bolus administration of either Xen2174 in a 5% dextrose solution or a 5% dextrose solution (Placebo), with no anatomical or pathological abnormalities that would compromise intrathecal lumbar injection. • Subject is willing and able to remain at the research center for the entire 3-day Treatment Period. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Subject is pregnant or lactating. • Subject has been on an investigational drug within 30 days prior to the initiation of Study Drug. • Subject has had prior exposure to Study Drug in a previous clinical trial. • Subject has a condition that would contraindicate the use of opioid analgesia, particularly chronic respiratory compromise. • Subject is morbidly obese (body mass index = 35 kg/m2 ). • Subject has chronic respiratory insufficiency. • Subject is on chronic opioid therapy, or is opioid tolerant in the judgment of the Investigator because of routine opioid use. • Subject has a known allergy or hypersensitivity to opioids, paracetamol and/or ondansetron. • Subject has known bleeding disorder or is taking agents affecting coagulation preoperatively [deep vein thrombosis (DVT) prophylaxis is of the Investigator’s choice postoperatively]. • Subject has any other condition or factor, such as an intracranial lesion associated with increased intracranial pressure, cognitive impairment or mental illness, which in the opinion of the Investigator might increase the risk to the subject or that precludes the subject’s ability to adhere to the protocol procedures. • Subject has a known or suspected history of substance or alcohol abuse within 2 years prior to Screening, or is currently using alcohol, drugs of abuse, or any prescription, or over-the-counter medication, in a manner that the Investigator considers indicative of abuse/dependence. • Subject tests positive to drug screens – amphetamines, methamphetamines (including MDMA/3,4-methylenedioxymethamphetamine), barbiturates, benzodiazepines, THC/marijuana, cocaine and its metabolites (e.g., benzoylecgonine), morphine and its related metabolites derived from opium (opiates), opioids, methadone, PCP (phencyclidine/phenylcyclohexylpiperidine), tricyclic antidepressants – that cannot be justified by prescription use. • Subject is receiving central nervous system (CNS) drugs for pain, such as a selective serotonin reuptake inhibitor (SSRI), a selective norepinephrine receptor inhibitor (SNRI), monoamine oxidase inhibitor (MAOI), carbamazepine, or tricyclic amine (TCA) compounds within 1-month prior to Check-In. [Note: if subject is on stable dose of SSRIs or SNRIs for 6 weeks prior to Screening and for a diagnosis other than relief of pain, then they may be eligible for participation in the trial, providing stable doses of the medications are maintained postoperatively]. • Subject has a documented history of seizure, prior head injury resulting in unconsciousness, or has been prescribed anti-seizure medication.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of two dose levels of Xen2174 on the area-under-the-curve of Numeric Rating Scale (NRS) pain scores in the period 0-48 hours following bunionectomy surgery.;Secondary Objective: The evaluation of: • Time to onset of moderate to severe pain following surgery. • Opioid consumption during the following periods: 0-48 hours post surgery, Day 3 post surgery, and Week 1 post discharge (i.e., Day 4 to Day 10 post surgery). • Assess the safety and tolerability of Xen2174 in the acute pain setting. • Explore the dose-effect relationship of Xen2174. • Evaluate the systemic single-dose pharmacokinetic (PK) profiles of single-dose IT Xen2174. • Estimate the duration of efficacy of Xen2174.;Primary end point(s): Area-under-the-curve of Numeric Rating Scale (NRS) pain scores in the period 0-48 hours following surgery.;Timepoint(s) of evaluation of this end point: Pain scores during the first 48 hours following surgery. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Time to onset of moderate to severe pain. • Total amount of opiate analgesia consumed during the Treatment Period;Timepoint(s) of evaluation of this end point: Days 1 through 3 following surgery. | — |
Countries
Bulgaria
Contacts
Public ContactEnquiries
Xenome Ltd
Outcome results
None listed