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

NCT04429919 | Completed Phase 2 DMC

• 1 other identifier: AP-325.04
• Study Type: interventional
• Target: 99
• Locations: 5 countries
• Sites: 32

Brief 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-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).

Conditions

Peripheral Post-surgical Neuropathic Pain

Keywords

AP-325; Phase IIa; PPNP; post-surgical neuropathic pain

Outcome Measures

Primary Outcomes (1)

• Change from Baseline to Day 10 in the 5-day average pain intensity score based on the Pain Intensity Numerical Rating Scale (PI-NRS; ranges from "no pain" = 0 to "the worst possible pain" = 10; the lower the score, the better the outcome)

  The 5-day average pain intensity score based on the Pain Intensity Numerical Rating Scale (PI-NRS) will be assessed to investigate the efficacy of repeat oral dosing of AP-325

  Baseline to Day 10

Secondary Outcomes (25)

• Longitudinal analysis of the 5-day average PI-NRS score (ranges from "no pain" = 0 to "the worst possible pain" = 10; the lower the score, the better the outcome) over time from Baseline until Day 35

  Baseline to Day 35

• Changes from Baseline in the 5-day average PI-NRS score (change can be in the range of 0 to 10; the bigger the change towards lower PI-NRS scores, the better the outcome) (from Baseline to Day 5, 15, 20, 25, 30 and 35)

  Baseline to Day 5, 15, 20, 25, 30 and 35

• Responder rate: proportion of subjects who have a ≥30% reduction in the 5-day average PI-NRS score (in the range of 0 to 10; the bigger the change towards lower scores, the better the outcome) relative to Baseline (on Days 5, 10, 15, 25 and 35)

  Baseline to Day 5, 10, 15, 25 and 35

• Responder rate: proportion of subjects who have a ≥50% reduction in the 5-day average PI-NRS score (in the range of 0 to 10; the bigger the change towards lower scores, the better the outcome) relative to Baseline (on Days 5, 10, 15, 25 and 35)

  Baseline to Day 5, 10, 15, 25 and 35

• 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

  Days 3, 10, 15, and 36

Study Arms (2)

AP-325

EXPERIMENTAL

25 mg capsule for oral use, 4 capsules (100 mg) once daily in the morning before meals

Drug: AP-325

Placebo

PLACEBO COMPARATOR

4 capsules once daily in the morning before meals

Drug: Placebo

Interventions

AP-325 DRUG

During the 10-day double-blind treatment period (Days 1 to 10), subjects will take 4 capsules of the IMP orally once daily in the morning before breakfast.

AP-325

Placebo DRUG

During the 10-day double-blind treatment period (Days 1 to 10), subjects will take 4 capsules of the IMP orally once daily in the morning before breakfast.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be at least 18 years and not older than 80 years
• 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)
• 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)
• 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.
• 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
• 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)
• 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
• Subjects must understand the nature of the study procedures and provide written informed consent prior to any study-related procedures
• Body weight ≥55 kg for men and ≥50 kg for women
• Body mass index (BMI) \<40 kg/m²

You may not qualify if:

• 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
• 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
• Subjects using adjuvant chemotherapy or radiotherapy; adjuvant therapies must have been finished at least 4 weeks prior to the run-in period (Day -14)
• Creatinine clearance \<60 mL/min using the Cockcroft-Gault formula
• White blood cell count \<2500/mm³; neutrophil count \<1500/mm³; platelet count \<100 x 103/mm³
• Heart rate \<50 or \>100 beats per minute; systolic blood pressure \<100 or \>140 mmHg; diastolic blood pressure \<50 or \>90 mmHg after 5 minutes rest in supine position
• A history of multiple drug allergies
• History or presence of alcohol or drug abuse
• Subjects using strong opioids (e.g. a Morphine Equivalent Dose \[MED\] \>80 mg/day)
• Positive test for drugs of abuse at Day -7
• Evidence of depression and/or a score of ≥11 on the HADS depression subscale
• Any clinically relevant psychiatric disease in the past 5 years which is likely to interfere with the conduct of the study
• History of any clinically relevant liver disease within the last 6 months, or episodic/chronic migraine, or kidney dysfunction or disease
• Clinically significant gastrointestinal conditions, likely interfering with the study medication, study procedures or the outcome of the study
• Positive test for human immunodeficiency virus (HIV)

Sponsors & Collaborators

• Algiax Pharmaceuticals GmbH: lead
• FGK Clinical Research GmbH: collaborator

Study Sites (32)

UZ Antwerp

Edegem, 2650, Belgium

Location

Ziekenhuis Oost Limburg - campus St. Jan

Genk, 3600, Belgium

Location

AZ Sint-Lucas, Pijnkliniek

Ghent, 9000, Belgium

Location

Jessa ZH Hospital

Hasselt, 3500, Belgium

Location

UZ Leuven, Campus Pellenberg

Pellenberg, 3212, Belgium

Location

AZ Delta, Pijncentrum

Roeselare, 8800, Belgium

Location

Neurology and Physiotherapy Outpatient Clinic Skopalíkova

Brno, 61500, Czechia

Location

NEUROHK, s.r.o.

Choceň, 56501, Czechia

Location

ALGOMED s.r.o. - Centrum léčby bolesti

České Budějovice, 370 01, Czechia

Location

Neuros, s.r.o.

Pilsen, 301 00, Czechia

Location

Praglandia, s.r.o.

Prague, 150 00, Czechia

Location

MP-neuro s.r.o., Poliklinika Modrý pavilon

Slezská Ostrava, 71000, Czechia

Location

CHU Amiens-Picardie, Centre de Recherche Clinique

Amiens, 80054, France

Location

Institut de Cancerologie de l'Ouest, Anesthésie/Douleur

Angers, 49055, France

Location

Hopital Ambroise Paré, Centre d'évaluation et de traitement de la douleur

Boulogne, 92100, France

Location

CHD Vendée, Département d'évaluation et du traitement de la douleur

La Roche-sur-Yon, 85925, France

Location

Polyclinique de Limoges - Site Chenieux, Centre d'Evaluation et de traitement de la Douleur

Limoges, 87000, France

Location

Hopîtal Cochin, Centre d'évaluation et du traitement de la douleur

Paris, 75014, France

Location

emovis GmbH, Dedicated Study Site

Berlin, 10629, Germany

Location

Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH, (Ruhr-Universität Bochum) Neurologische Klinik und Poliklinik

Bochum, 44789, Germany

Location

Kliniken der Stadt Köln gGmbH, Krankenhaus Köln-Merheim, Lungenklinik am Zentrum für Thoraxchirurgie, Pneumologie/ Onkologie, Schlaf- und Beatmungsmedizin, Klinikum der Universität Witten/Herdecke

Cologne, 51109, Germany

Location

Florence-Nightingale-Krankenhaus der Kaiserswerther Diakonie, Klinik für Thoraxchirurgie

Düsseldorf, 40489, Germany

Location

Universitätsklinikum Würzburg, Klinik und Poliklinik für Anästhesiologie, Zentrum für Interdisziplinäre Schmerzmedizin

Würzburg, 97078, Germany

Location

HOSPITAL DEL MAR.#Cod. CNH: 080057#

Barcelona, 08003, Spain

Location

HOSPITAL UNIVERSITARIO PUERTA DEL MAR#Cod. CNH: 110012#

Cadiz, 11009, Spain

Location

HOSPITAL UNIVERSITARI DE BELLVITGE#Cod. CNH: 080752#

L'Hospitalet de Llobregat, 08907, Spain

Location

HOSPITAL UNIVERSITARIO 12 DE OCTUBRE#Cod. CNH: 280035#

Madrid, 28041, Spain

Location

HOSPITAL UNIVERSITARIO LA PAZ#Cod. CNH: 280014#

Madrid, 28046, Spain

Location

HOSPITAL UNIVERSITARIO LA MORALEJA#Cod. CNH: 281179#

Madrid, 28050, Spain

Location

CLINICA UNIVERSIDAD DE NAVARRA#Cod. CNH: 310060#

Pamplona, 31008, Spain

Location

HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID#Cod. CNH: 281203#

Pozuelo de Alarcón, 28223, Spain

Location

HOSPITAL CLINICO UNIVERSITARIO DE VALENCIA#Cod. CNH: 460044#

Valencia, 46010, Spain

Location

Study Officials

• Heike Rittner, Prof. Dr.

  Universitätsklinikum Würzburg, Interdisziplinäre Schmerzmedizin, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: placebo controlled, Phase IIa clinical trial

Study Record Dates

• First Submitted: May 29, 2020
• First Posted: June 12, 2020
• Study Start: June 22, 2020
• Primary Completion: October 4, 2024
• Study Completion: October 4, 2024
• Last Updated: October 16, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (9); FR (6); BE (6); CZ (6); DE (5)