AP-325 in Subjects With Peripheral Post-surgical Neuropathic Pain

• Status: Recruiting
• Trial end date: 2022-02-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase IIa randomized, double-blind, placebo-controlled study. The study objective is to investigate the efficacy and safety of repeat oral dosing of the investigational medicinal product (IMP) AP-325 for the treatment of peripheral post-surgical neuropathic pain (PPNP) after breast surgery (breast cancer interventions), chest surgery (i.e. thoracotomy, video assisted thoracoscopy and sternotomy) or groin hernia repair (i.e. femoral hernia repairs and inguinal hernia repairs).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Algiax Pharmaceuticals GmbH
• Collaborator: FGK Clinical Research GmbH

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 (breast cancer interventions), chest surgery (i.e. thoracotomy, video assisted thoracoscopy and sternotomy) or groin hernia repair (i.e. femoral hernia repairs and inguinal hernia repairs)

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) <35 kg/m²

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

3. Subjects diagnosed with chronic post-surgical neuropathic pain with a disease duration exceeding 4 years

4. 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

5. Subjects using adjuvant chemotherapy or radiotherapy; adjuvant therapies must have been finished at least 4 weeks prior to the run-in period (Day -14)

6. Creatinine clearance <60 mL/min using the Cockcroft-Gault formula

7. White blood cell count <2500/mm³; neutrophil count <1500/mm³; platelet count <100 x 103/mm³

8. Heart rate <50 or >100 beats per minute; systolic blood pressure <100 or >140 mmHg; diastolic blood pressure <50 or >90 mmHg

9. A history of multiple drug allergies

10. History or presence of alcohol or drug abuse

11. Subjects using strong opioids (e.g. a Morphine Equivalent Dose [MED] >80 mg/day)

12. Positive test for drugs of abuse at Day -7

13. Evidence of depression and/or a score of ≥11 on the HADS depression subscale

14. Psychiatric disease in the past 5 years

15. History of any liver disease within the last 6 months, or migraine, or kidney dysfunction or disease (e.g. estimated glomerular filtration rate [eGFR] ≤30 mL/min per 1.73 m²)

16. Clinically significant gastrointestinal conditions, likely interfering with the study medication, study procedures or the outcome of the study

17. Positive test for human immunodeficiency virus (HIV)

18. Positive test for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C antibody and/or HIV1/HIV2 antibody at Screening

19. 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

20. Previous enrolment in this clinical study

21. Known hypersensitivity to the active substance or any of the excipients of the IMP or the rescue medication

22. Subjects dependent (as an employee or relative) on the sponsor or investigator

23. Subjects committed to an institution by virtue of an order issued either by the judicial or the administrative authorities

24. Legal incapacity or limited legal capacity

Randomization criteria

1. At least 5 daily pain assessments in the baseline week prior to randomization, with a mean score on the PI-NRS ≥4 and ≤9. Differences between the baseline daily pain scores on the PI-NRS must be ≤50%.

2. For female subjects of childbearing potential: negative pregnancy test in urine on Day 1.