Peripheral post-surgical neuropathic pain MedDRA version: 20.0 Level: LLT Classification code 10077974 Term: Peripheral neuropathic pain System Organ Class: 100000004852
Conditions
Interventions
Product Name: AP-325
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LAFLUNIMUS
CAS Number: 147076-36-6
Current Sponsor code: AP-325
Concentration unit: mg milligram(s)
Concentration type: equ
Sponsors
Algiax Pharmaceuticals GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects must be at least 18 years and not older than 80 years 2. Subjects with a diagnosis of chronic post-surgical neuropathic pain after breast surgery (e.g. breast-conserving surgery, mastectomy, surgery to remove lymph nodes), chest surgery (e.g. thoracotomy, video assisted thoracoscopy and sternotomy), hernia repair of the abdominal wall (e.g. femoral hernia repairs, inguinal hernia repairs, umbilical hernia repair or incisional hernia repair), abdominal surgery (e.g. cholecystectomy, appendectomy but also see exclusion criterion 15), varicose vein surgery or gynecologic surgery (e.g. hysterectomy, C-section) 3. The chronic post-surgical pain developed or increased in intensity after the surgical procedure and persisted beyond the healing process, i.e. at least 3 months after the initiating event, as defined according to the international association for the study of pain (IASP) classification of chronic pain for ICD-11 (Schug et al., 2019) 4. Subjects must have ‘probable’ or ‘definite’ neuropathic pain as assessed by the revised IASP special interest group on neuropathic pain (NeuPSIG) grading system (Finnerup et al., 2016) 5. Subjects must be willing and able to discontinue and washout prohibited substances including • pain medications (e.g. antidepressants, anticonvulsants/antiepileptics, selective serotonin and dual reuptake inhibitors, opioids, long-acting benzodiazepines, muscle relaxants, and topical analgesics), except the rescue medication, and • substances known to be inhibitors or inducers of CYP2C9 and inhibitors of CYP3A4 for specific washout periods of at least 5 times the drug half-life Note: Subjects using prohibited substances for other indications than neuropathic pain, e.g. antiepileptics for the treatment of epilepsy, may not be included in the study, because a discontinuation of such medication is not medically justifiable. 6. Permitted concomitant medications must have been stable for at least 4 weeks prior to Day -14 and any non-pharmacological therapies (e.g. physiotherapy, acupuncture and transcutaneous electrical neural stimulation) must have been initiated at least 3 weeks prior to Screening 7. Female subjects must not be pregnant or breastfeeding and be • of non-childbearing potential or • if of childbearing potential, use a highly effective contraceptive method from start of the IMP intake until 30 days after the last IMP intake and have a negative pregnancy test at Screening (blood test) 8. Male subjects must agree, from start of the IMP intake until 3 months after the last IMP intake, to refrain from donating sperm and use a male condom when having sexual intercourse with a woman of childbearing potential at any time and advise her to use a highly effective contraceptive method 9. Subjects must understand the nature of the study procedures and provide written informed consent prior to any study-related procedures 10. Body weight =55 kg for men and =50 kg for women 11. Body mass index (BMI) =65 years) y
Exclusion criteria
Exclusion criteria: 1. Subjects with neuropathic pain not a result of a surgical procedure as defined in inclusion criterion 2 2. Subjects with any other coexisting pain that cannot be discriminated from post-surgical neuropathic pain, in the opinion of the subject or clinician e.g., the pain is at least partially due to pain in deeper structures such as internal organs, joints, muscles or bones. 3. Inability to participate in the study, in the opinion of the investigator, because of, for example, severe brain damage, language barrier, dementia, or other clinically significant or unstable conditions 4. Subjects using adjuvant chemotherapy or radiotherapy; adjuvant therapies must have been finished at least 4 weeks prior to the run-in period (Day -14) 5. Creatinine clearance 100 beats per minute; systolic blood pressure 140 mmHg; diastolic blood pressure 90 mmHg after 5 minutes rest in supine position 8. A history of multiple drug allergies 9. History or presence of alcohol or drug abuse 10. Subjects using strong opioids (e.g. a Morphine Equivalent Dose [MED] >80 mg/day) 11. Positive test for drugs of abuse at Day -7 12. Evidence of depression and/or a score of =11 on the HADS depression subscale 13. Any clinically relevant psychiatric disease in the past 5 years which is likely to interfere with the conduct of the study 14. History of any clinically relevant liver disease within the last 6 months, or episodic/chronic migraine, or kidney dysfunction or disease 15. Clinically significant gastrointestinal conditions, likely interfering with the study medication, study procedures or the outcome of the study 16. Positive test for human immunodeficiency virus (HIV) 17. Positive test for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C antibody and/or HIV1/HIV2 antibody at Screening 18. Participation of subject in an interventional clinical study within 1 month or, if applicable, 5 half-lives of the IMP, whatever is longer, before Screening or during participation in this study 19. Subjects who were previously enrolled in this clinical study and have taken study medication or terminated due to poor compliance 20. Known hypersensitivity to the active substance or any of the excipients of the IMP or the rescue medication 21. Subjects dependent (as an employee or relative) on the sponsor or investigator 22. Subjects committed to an institution by virtue of an order issued either by the judicial or the administrative authorities 23. Legal incapacity or limited legal capacity
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the efficacy of repeat oral dosing of AP-325 on neuropathic pain in subjects with peripheral post-surgical neuropathic pain (PPNP) after 10 days of treatment;Secondary Objective: - To further investigate the long-lasting efficacy of repeat oral dosing of AP-325 on neuropathic pain over the entire study duration - To investigate the effect of repeat oral dosing of AP-325 on patient-reported outcomes - To investigate the effect of repeat oral dosing of AP-325 on the use of rescue medication - To investigate the effect of repeat oral dosing of AP-325 on the proportion of subjects classified as treatment failure - To investigate the safety and tolerability of repeat oral dosing of AP-325 in subjects with PPNP - To evaluate plasma concentrations of AP-325 - To evaluate investigational medicinal product (IMP) concentration-effect relationships - To evaluate the effect of CYP2C9 polymorphisms on the plasma concentration of AP-325;Primary end point(s): Change from Baseline to Day 10 in the 5-day average pain intensity score based on the Pain Intensity Numerical Rating Scale (PI-NRS);Timepoint(s) of evaluation of this end point: Baseline to Day 10 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Longitudinal analysis of the 5-day average PI-NRS score over time from Baseline until Day 35 2. Changes from Baseline in the 5-day average PI-NRS score (from Baseline to Day 5, 15, 20, 25, 30 and 35) 3. Responder rate: proportion of subjects who have a =30% reduction in the 5-day average PI-NRS score relative to Baseline (on Days 5, 10, 15, 25 and 35) 4. Responder rate: proportion of subjects who have a =50% reduction in the 5-day average PI-NRS score relative to Baseline (on Days 5, 10, 15, 25 and 35) 5. Proportion of subjects who "much improved" or "very much improved" relative to Baseline on the patient global impression of change (PGIC) on Days 3, 10, 15, and 36 6. Changes from Baseline in the neuropathic pain evaluation using the neuropathic pain symptom inventory (NPSI) questionnaire on Days 3, 10, 15, and 36 7. Changes from Baseline in the 5-day average daily sleep interference scale (DSIS) score (from Baseline to Day 5, 10, 15, 25 and 35) 8. Changes from Baseline in the anxiety and depression assessment using the hospital anxiety and depression scale (HADS) on Days 10 and 36 9. Time to first use of rescue medication after randomization 10. Total amount of rescue medication use (in mg per day) after randomization 11. Proportion of subjects classified as treatment failure and time to classification as treatment failure after randomization 12. Incidence, severity and seriousness of treatment-emergent adverse events (TEAEs) 13. Changes from Baseline in physical examination and vital signs 14. Changes from Baseline in safety laboratory 15. Changes from Baseline in 12-lead electrocardiogram 16. Changes from Baseline in body weight 17. Plasma concentrations of AP-325 at 1 hour post-dose on Days 1 and 10; pre-dose on Days 3 and 10; and on Day 36 18. Accumulation of Ctrough from Day 3 to Day 10 19. Relationship between Ctrough-ss (Day 10) and the change from Baseline to Day 10 in the 5-day average pain intensity score based on the PI-NRS 20 | — |
Countries
Czechia, Czech Republic, Germany, Spain
Contacts
Public ContactChief Scientific Officer
Algiax Pharmaceuticals GmbH
Outcome results
None listed