Peripheral Post-surgical Neuropathic PainPhase 2NCT04429919
AP-325 in Subjects With Peripheral Post-surgical Neuropathic Pain
A Phase 2 study testing AP-325 in people with Peripheral Post-surgical Neuropathic Pain, run by Algiax Pharmaceuticals GmbH at 32 sites in 5 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Peripheral Post-surgical Neuropathic Pain
- What is being tested?
- AP-325
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 99 participants
- Where
- 32 sitesin 5 countries
- Study dates
- 22 Jun 2020to 4 Oct 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must be at least 18 years and not older than 80 years
- 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)
- 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
Show all 15Show fewer
- 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
Who cannot join
- Subjects with neuropathic pain not a result of a surgical procedure as defined in inclusion criterion 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
- 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
Show all 26Show fewer
- 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)
- Positive test for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C antibody and/or HIV1/HIV2 antibody at Screening
- 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
- Subjects who were previously enrolled in this clinical study and have taken study medication or terminated due to poor compliance
- Known hypersensitivity to the active substance or any of the excipients of the IMP or the rescue medication
- Subjects dependent (as an employee or relative) on the sponsor or investigator
- Subjects committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
- Legal incapacity or limited legal capacity
- Randomization criteria
- 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%.
- For female subjects of childbearing potential: negative pregnancy test in urine on Day 1.
Trial locations and contacts
32 sites in 5 countries.
32 sites in 5 countries
Spain9 sites
HOSPITAL DEL MAR.#Cod. CNH: 080057#
Barcelona, 08003
HOSPITAL UNIVERSITARIO PUERTA DEL MAR#Cod. CNH: 110012#
Cadiz, 11009
HOSPITAL UNIVERSITARI DE BELLVITGE#Cod. CNH: 080752#
L'Hospitalet de Llobregat, 08907
HOSPITAL UNIVERSITARIO 12 DE OCTUBRE#Cod. CNH: 280035#
Madrid, 28041
HOSPITAL UNIVERSITARIO LA PAZ#Cod. CNH: 280014#
Madrid, 28046
HOSPITAL UNIVERSITARIO LA MORALEJA#Cod. CNH: 281179#
Madrid, 28050
CLINICA UNIVERSIDAD DE NAVARRA#Cod. CNH: 310060#
Pamplona, 31008
HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID#Cod. CNH: 281203#
Pozuelo de Alarcón, 28223
HOSPITAL CLINICO UNIVERSITARIO DE VALENCIA#Cod. CNH: 460044#
Valencia, 46010
Belgium6 sites
UZ Antwerp
Edegem, 2650
Ziekenhuis Oost Limburg - campus St. Jan
Genk, 3600
AZ Sint-Lucas, Pijnkliniek
Ghent, 9000
Jessa ZH Hospital
Hasselt, 3500
UZ Leuven, Campus Pellenberg
Pellenberg, 3212
AZ Delta, Pijncentrum
Roeselare, 8800
Czechia6 sites
Neurology and Physiotherapy Outpatient Clinic Skopalíkova
Brno, 61500
ALGOMED s.r.o. - Centrum léčby bolesti
České Budějovice, 370 01
NEUROHK, s.r.o.
Choceň, 56501
Neuros, s.r.o.
Pilsen, 301 00
Praglandia, s.r.o.
Prague, 150 00
MP-neuro s.r.o., Poliklinika Modrý pavilon
Slezská Ostrava, 71000
France6 sites
CHU Amiens-Picardie, Centre de Recherche Clinique
Amiens, 80054
Institut de Cancerologie de l'Ouest, Anesthésie/Douleur
Angers, 49055
Hopital Ambroise Paré, Centre d'évaluation et de traitement de la douleur
Boulogne, 92100
CHD Vendée, Département d'évaluation et du traitement de la douleur
La Roche-sur-Yon, 85925
Polyclinique de Limoges - Site Chenieux, Centre d'Evaluation et de traitement de la Douleur
Limoges, 87000
Hopîtal Cochin, Centre d'évaluation et du traitement de la douleur
Paris, 75014
Germany5 sites
emovis GmbH, Dedicated Study Site
Berlin, 10629
Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH, (Ruhr-Universität Bochum) Neurologische Klinik und Poliklinik
Bochum, 44789
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
Florence-Nightingale-Krankenhaus der Kaiserswerther Diakonie, Klinik für Thoraxchirurgie
Düsseldorf, 40489
Universitätsklinikum Würzburg, Klinik und Poliklinik für Anästhesiologie, Zentrum für Interdisziplinäre Schmerzmedizin
Würzburg, 97078
About this study
Official title: A Randomized, Double-blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of AP-325 in Subjects With Peripheral Post-surgical Neuropathic Pain
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).
Read the detailed description
This is a Phase IIa randomized, double-blind, placebo controlled, parallel group study to evaluate the efficacy (by changes in Pain Intensity Numerical Rating Scale [PI-NRS]) and safety (by monitoring adverse events) of AP-325 in subjects with PPNP.
The clinical trial will be conducted in Germany, Spain, Czech Republic, Belgium and France.
Eligible subjects will undergo a 2-week run-in period consisting of a washout-period of prohibited medications in the 1st week and a baseline period in the 2nd week. If subjects have at least 5 self-reported pain assessments in the baseline period (documented in a diary) and meet the required pain criteria, they will be randomized to AP-325 or placebo in a 1:1 ratio.
Subjects will take the IMP (AP-325 or placebo) for 10 days (double-blind treatment period; Days 1-10) and then be followed up for a further 26 days (drug-free period; Days 11-36). An end of study visit will be performed on Day 36.
At least 96 subjects (48 for each treatment) need to be analyzed for the primary endpoint at Day 10 to reach the power estimate (120 subjects should be screened for the study).
AP-325 100 mg (4 x 25 mg capsules) or Placebo (4 capsules) will be orally taken once daily in the morning before meals for 10 consecutive days.
Pain will be assessed, and quality of life will be investigated using standardized and validated questionnaires [Pain Intensity Numerical Rating Scale (PI-NRS), patient global impression of change (PGIC), neuropathic pain symptom inventory (NPSI) questionnaire, daily sleep interference scale (DSIS) score, hospital anxiety and depression scale (HADS)].
- Being tested
- AP-325, Placebo
- Keywords
- AP-325, Phase IIa, PPNP, post-surgical neuropathic pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AP-325Drug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| AP-325 | Experimental | 25 mg capsule for oral use, 4 capsules (100 mg) once daily in the morning before meals Receives: Drug: AP-325 |
| Placebo | Placebo comparator | 4 capsules once daily in the morning before meals Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
The 5-day average PI-NRS score will be assessed to investigate the long-lasting efficacy of repeat oral dosing of AP-325 on neuropathic pain over the entire study duration
Measured: 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)
The 5-day average PI-NRS score will be assessed
Measured: 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)
The responder rate will be compared between treatments on Day 5, 10, 15, 25 and 35
Measured: 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)
The responder rate will be compared between treatments on Day 5, 10, 15, 25 and 35
Measured: 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
The PGIC will be dichotomized into treatment success (i.e. scoring 'much improved' or 'very much improved').
Measured: Days 3, 10, 15, and 36
Changes from Baseline in the neuropathic pain evaluation using the neuropathic pain symptom inventory (NPSI; ranges from "no pain" = 0 to "the worst possible pain" = 120; the lower the score, the better) questionnaire on Days 3, 10, 15, and 36
Neuropathic pain symptom inventory (NPSI) questionnaire to assess the neuropathic pain of the patients
Measured: Baseline, Day 3, 10, 15 and 36
Changes from Baseline in the 5-day average daily sleep interference scale (DSIS; ranges from "pain does not interfere with sleep" = 0 to "pain completely interferes with sleep" = 10) score (from Baseline to Day 5, 10, 15, 25 and 35)
The 5-day average daily sleep interference scale (DSIS) score will be assessed
Measured: Baseline to Day 5, 10, 15, 25 and 35
Changes from Baseline in the anxiety and depression assessment using the hospital anxiety and depression scale (HADS; subscales range from 0 to 21, with higher values indicating higher anxiety or depression; the lower the score) on Days 10 and 36
The hospital anxiety and depression scale (HADS) to assess the anxiety and depression of the patients
Measured: Baseline, Day 10 and 36
Time to first use of rescue medication after randomization
The time to first use of rescue medication after randomization will be analyzed
Measured: A priori specification not possible, between Day 1 until Day 36
Total amount of rescue medication use (in mg per day) after randomization
The total amount of rescue medication (i.e. the total mg of rescue medication per day will be tabulated
Measured: A priori specification not possible, between Day 1 until Day 36
Proportion of subjects classified as treatment failure
Proportion of subjects classified as treatment failure at least once after randomization will be tabulated
Measured: A priori specification not possible, between Day1 and Day 36
Time to classification as treatment failure after randomization
Time to first classification as treatment failure after randomization will be analyzed
Measured: A priori specification not possible, between Day1 and Day 36
Incidence, severity and seriousness of treatment-emergent adverse events (TEAEs)
All TEAEs occurring during the clinical trial will be registered, documented and evaluated
Measured: A priori specification not possible, between Day1 and Day 36
Incidence of abnormal physical examinations
Abnormal physical examination results will be evaluated and reported as AEs
Measured: Baseline, Day 3, 10, 15 and 36
Changes from Baseline in vital signs: Systolic and diastolic blood pressure
Systolic and diastolic blood pressure will be measured
Measured: Baseline, Day 1, 3, 10, 15 and 36
Changes from Baseline in vital signs: Heart rate
Heart rate will be measured
Measured: Baseline, Day 1, 3, 10, 15 and 36
Changes from Baseline in vital signs: Respiratory rate
Respiratory rate will be measured
Measured: Baseline, Day 1, 3, 10, 15 and 36
Changes from Baseline in vital signs: Aural body temperature
Aural body temperature will be measured
Measured: Baseline, Day 1, 3, 10, 15 and 36
Incidence of abnormal laboratory test results
Abnormal laboratory test results will be evaluated
Measured: Baseline, Day 3, 10, 15 and 36
Incidence of abnormal ECG readings
Abnormal 12 lead ECG readings will be evaluated
Measured: Baseline, Day 3, 10 and 36
Changes from Baseline in body weight
Body weight will be evaluated
Measured: Baseline, Day 10 and 36
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
Plasma concentrations of AP-325 will be evaluated
Measured: Days 1, 3, 10 and 36
Accumulation of Ctrough from Day 3 to Day 10
Plasma concentrations of AP-325 will be evaluated
Measured: Day 3 and 10
Correlation 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
AP-325 concentration-effect relationships will be evaluated
Measured: Baseline to Day 10
Correlation between CYP2C9 genotype and the metabolism of AP-325 (optional)
The effect of CYP2C9 polymorphisms (determined by CYP2C9 genotyping) on the plasma concentration of AP-325 will be evaluated
Measured: Day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2020
- Study start22 Jun 2020
- Primary completion4 Oct 2024
- Study completion4 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Peripheral Post-surgical Neuropathic PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- placebo controlled, Phase IIa clinical trial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 99 participants (actual)
Sponsor and investigators
- Lead sponsor
- Algiax Pharmaceuticals GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- FGK Clinical Research GmbH
- Responsible party
- Sponsor
- Investigators
- Heike Rittner, Prof. Dr., Principal investigator, Universitätsklinikum Würzburg, Interdisziplinäre Schmerzmedizin, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04429919
- Sponsor's protocol ID
- AP-325.04
- Status last verified
- Oct 2024
- First submitted
- 29 May 2020
- Last updated
- 16 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of AP-325 in Subjects With Peripheral Post-surgical Neuropathic Pain
- ClinicalTrials.gov ID
- NCT04429919
- Acronym / sponsor ID
- AP-325.04
- Keywords
- AP-325, Phase IIa, PPNP, post-surgical neuropathic pain
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 99 participants (actual)
- Lead sponsor
- Algiax Pharmaceuticals GmbHIndustry (pharma, biotech, devices)
- Collaborators
- FGK Clinical Research GmbH
- Study start
- 22 Jun 2020 (actual)
- Primary completion
- 4 Oct 2024 (actual)
- Study completion
- 4 Oct 2024 (actual)
- First posted
- 12 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
This is a Phase IIa randomized, double-blind, placebo controlled, parallel group study to evaluate the efficacy (by changes in Pain Intensity Numerical Rating Scale [PI-NRS]) and safety (by monitoring adverse events) of AP-325 in subjects with PPNP.
The clinical trial will be conducted in Germany, Spain, Czech Republic, Belgium and France.
Eligible subjects will undergo a 2-week run-in period consisting of a washout-period of prohibited medications in the 1st week and a baseline period in the 2nd week. If subjects have at least 5 self-reported pain assessments in the baseline period (documented in a diary) and meet the required pain criteria, they will be randomized to AP-325 or placebo in a 1:1 ratio.
Subjects will take the IMP (AP-325 or placebo) for 10 days (double-blind treatment period; Days 1-10) and then be followed up for a further 26 days (drug-free period; Days 11-36). An end of study visit will be performed on Day 36.
At least 96 subjects (48 for each treatment) need to be analyzed for the primary endpoint at Day 10 to reach the power estimate (120 subjects should be screened for the study).
AP-325 100 mg (4 x 25 mg capsules) or Placebo (4 capsules) will be orally taken once daily in the morning before meals for 10 consecutive days.
Pain will be assessed, and quality of life will be investigated using standardized and validated questionnaires [Pain Intensity Numerical Rating Scale (PI-NRS), patient global impression of change (PGIC), neuropathic pain symptom inventory (NPSI) questionnaire, daily sleep interference scale (DSIS) score, hospital anxiety and depression scale (HADS)].
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- placebo controlled, Phase IIa clinical trial
| Arm | Type | Receives |
|---|---|---|
| AP-325 | Experimental | Drug: AP-32525 mg capsule for oral use, 4 capsules (100 mg) once daily in the morning before meals |
| Placebo | Placebo comparator | Drug: Placebo4 capsules once daily in the morning before meals |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Subjects must be at least 18 years and not older than 80 years
- 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)
- 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
Key exclusion criteria (26 listed)
- Subjects with neuropathic pain not a result of a surgical procedure as defined in inclusion criterion 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
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AP-325During 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. | Drug | AP-325 |
| PlaceboDuring 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. | Drug | Placebo |
Primary outcome
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)
Time frame: Baseline to Day 10
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
25 secondary outcomes
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
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: Days 3, 10, 15, and 36
Changes from Baseline in the neuropathic pain evaluation using the neuropathic pain symptom inventory (NPSI; ranges from "no pain" = 0 to "the worst possible pain" = 120; the lower the score, the better) questionnaire on Days 3, 10, 15, and 36
Time frame: Baseline, Day 3, 10, 15 and 36
Changes from Baseline in the 5-day average daily sleep interference scale (DSIS; ranges from "pain does not interfere with sleep" = 0 to "pain completely interferes with sleep" = 10) score (from Baseline to Day 5, 10, 15, 25 and 35)
Time frame: Baseline to Day 5, 10, 15, 25 and 35
Changes from Baseline in the anxiety and depression assessment using the hospital anxiety and depression scale (HADS; subscales range from 0 to 21, with higher values indicating higher anxiety or depression; the lower the score) on Days 10 and 36
Time frame: Baseline, Day 10 and 36
Time to first use of rescue medication after randomization
Time frame: A priori specification not possible, between Day 1 until Day 36
Total amount of rescue medication use (in mg per day) after randomization
Time frame: A priori specification not possible, between Day 1 until Day 36
Proportion of subjects classified as treatment failure
Time frame: A priori specification not possible, between Day1 and Day 36
Time to classification as treatment failure after randomization
Time frame: A priori specification not possible, between Day1 and Day 36
Incidence, severity and seriousness of treatment-emergent adverse events (TEAEs)
Time frame: A priori specification not possible, between Day1 and Day 36
Incidence of abnormal physical examinations
Time frame: Baseline, Day 3, 10, 15 and 36
Changes from Baseline in vital signs: Systolic and diastolic blood pressure
Time frame: Baseline, Day 1, 3, 10, 15 and 36
Changes from Baseline in vital signs: Heart rate
Time frame: Baseline, Day 1, 3, 10, 15 and 36
Changes from Baseline in vital signs: Respiratory rate
Time frame: Baseline, Day 1, 3, 10, 15 and 36
Changes from Baseline in vital signs: Aural body temperature
Time frame: Baseline, Day 1, 3, 10, 15 and 36
Incidence of abnormal laboratory test results
Time frame: Baseline, Day 3, 10, 15 and 36
Incidence of abnormal ECG readings
Time frame: Baseline, Day 3, 10 and 36
Changes from Baseline in body weight
Time frame: Baseline, Day 10 and 36
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
Time frame: Days 1, 3, 10 and 36
Accumulation of Ctrough from Day 3 to Day 10
Time frame: Day 3 and 10
Correlation 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
Time frame: Baseline to Day 10
Correlation between CYP2C9 genotype and the metabolism of AP-325 (optional)
Time frame: Day 3
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2024.
- Individual participant dataSharing planned: No
Related trials for Peripheral Post-surgical Neuropathic Pain
Not yet recruitingPhase 1
Simultaneous Engagement of Networks for Alleviating Pain (SENAP)
Neuropathic Pain, Postherpetic Neuralgia
Recruiting
Comparison of Two Postoperative Care Strategies After Breast Surgery
Postoperative Pain, Pain Management
Recruiting
Intraoperative Lidocaine or Dexmedetomidine for Postoperative Pain Modulation After Urethral Reconstruction.
Urethral Stricture
RecruitingObservational study
Decompression of Pudendal and Inferior Cluneal Nerves Using Robot-assisted Laparoscopy for Entrapment Neuralgias : the X-DECO Study
Pudendal Neuralgia
Not yet recruitingPhase 2
NAC-REPAIR for Post-surgical Pain
Carpal Tunnel Surgery, Trigger Finger Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Heike Rittner, Prof. Dr. principal investigator
Universitätsklinikum Würzburg, Interdisziplinäre Schmerzmedizin, Germany
32 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AP-325 in people with Peripheral Post-surgical Neuropathic Pain, run by Algiax Pharmaceuticals GmbH at 32 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in Spain, Belgium, Czechia, France, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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) (time frame: Baseline to Day 10). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2024.