The safety, tolerability, and efficacy of PN6047 HCl in peripheral neuropathic pain characterized by mechanical allodynia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pharmnovo AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2025-09-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To investigate the safety and tolerability of PN6047 HCl in participants having peripheral neuropathic pain with mechanical allodynia (NPMA).

Secondary objectives 3

1. To investigate the analgesic efficacy of 20 days of oral administration of PN6047 HCl compared to placebo in participants with NPMA
2. To investigate the efficacy of PN6047 HCl on the intensity (NRS, 0-10) and area of dynamic mechanical allodynia, compared to placebo in participants with NPMA
3. To investigate the systemic exposure to PN6047 HCl and potentially its metabolites

Conditions and MedDRA coding

Mechanical allodynia

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, Danish Medicines Agency, Finnish Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Provision of informed consent prior to any trial-related procedures.
2. Male, or female participants 18-70 years of age at the time of Visit 1.
3. Body mass index 18.5-35.0 kg/m2.
4. Diagnosis of neuropathic pain, either “probable” or “definite” according to the Neuropathic Pain Special Interest Group grading system
5. At least 3 months duration of neuropathic pain.
6. Defined aetiology of neuropathic pain; either diabetic neuropathy, post-herpetic neuralgia, or peripheral nerve injury due to trauma, compression, or surgery. The anatomical level of nerve injury must be specified, i.e., radiculopathy, polyneuropathy, or mononeuropathy (also naming the injured nerve(s) in the latter case). Complex regional pain syndrome type 2 can be included, provided the anatomical criteria above are met.
7. At Visit 1, intensity of usual pain of ≥4 and ≤9 on the Numerical Rating Scale (NRS). At Visit 3, average pain intensity of ≥4 and ≤9 on the NRS over the preceding 5 days. Participants must also complete at least 7 of 10 pain diary entries in the 5 days prior to Visit 3.
8. Dynamic mechanical allodynia at Screening and Visit 3 with an intensity ≥4 and ≤9 (NRS) and/or Touch-Evoked Pain at Screening and mean 5-day Baseline Touch-Evoked Pain ≥4 and ≤9 (NRS).
9. If applicable, washout of prohibited medication must be completed at least 5 days prior to Visit 3.
10. Trial participant finds the capsule (size 0) acceptable to swallow.
11. Women of childbearing potential (WOCBP) must agree to use a highly effective method of contraception with a failure rate of <1% to prevent pregnancy. Such methods include: a) practicing abstinence (only allowed when this is the preferred and usual lifestyle of the participant), b) having a vasectomized partner, c) having bilateral tubal ligation or occlusion, d) combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable), intrauterine device or intrauterine hormone-releasing system, from at least 30 days prior to first dose to 30 days after last dose of trial intervention. Their male partner must agree to use a condom during the same time frame if they have not undergone vasectomy.
12. Women of non-childbearing potential (WONCBP) can participate and are defined as premenopausal females who have undergone hysterectomy, bilateral oophorectomy or bilateral salpingectomy; or are postmenopausal, defined as 12 consecutive months of spontaneous amenorrhoea without an alternative medical cause, and a follicle-stimulating hormone level above the reference range of 25-140 IU/L, except in persons using hormonal contraception or hormone replacement therapy (HRT). Persons receiving HRT and whose menopausal status is in doubt will be required to use one of the nonhormonal, highly effective contraception methods if they wish to continue their HRT during the trial. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status before trial enrolment.
13. Male participants must either be willing to use condom or practice sexual abstinence during treatment intervention and until 30 days after last dose of trial intervention; or to have been vasectomized, to prevent pregnancy and drug exposure of a partner. If using a condom, their female partner of childbearing potential must use contraceptive methods with a failure rate of <1% to prevent pregnancy (see above).
14. WOCBP must not plan to get pregnant or donate eggs, during the trial and for at least 3 months after the final trial intervention dose. Male participants must refrain from donating sperm from the first dose of trial intervention until 3 months after with the last dose of the trial intervention.
15. Ability to comply with the requirements of the trial, as judged by the Investigator.

Exclusion criteria 17

1. Participation in another clinical trial with an investigational drug within 30 days of Screening.
2. Currently pregnant or lactating.
3. Other pain that may confound assessment of neuropathic pain, e.g., significant musculoskeletal pain, neck/low back pain, as judged by the Investigator.
4. Neuropathic pain caused by CNS injury, e.g., stroke, spinal cord injury, multiple sclerosis.
5. Severe or unstable medical (e.g., malignancy, cardiovascular, hepatic, renal) or psychiatric disease (e.g., depression requiring treatment) which may interfere with the trial objectives or the safety of the participant, as judged by the Investigator.
6. Diagnosis or history of epilepsy.
7. History or risk of falling incidents, as judged by the Investigator
8. After 10 min supine rest, vital signs outside any the following ranges: Systolic blood pressure (BP) 90-170mmHg, diastolic BP >100mmHg, or oxygen saturation (SpO2) below 90%. A value outside the range should be repeated after a 10 min interval. If that value is still outside the range, it is confirmed; otherwise not.
9. Clinically significant abnormality on 12-lead ECG (median of triplicate), including prolonged QTcF (>450 msec men or >470 msec women).
10. Clinically significant laboratory test value abnormalities, as judged by the Investigator, including: a. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5 × upper limit of normal (ULN) or b. Bilirubin >1 × ULN or c. Creatinine clearance <60 mL/min (Cockcroft-Gault method)
11. History of alcohol or drug abuse within 2 years of entering the trial.
12. History of, or positive test for human immunodeficiency virus (HIV), hepatitis B or C.
13. Positive urine toxicology test for drugs with potential of dependence/abuse (including cannabinoids).
14. Never used an opioid with an effect on the MOR, including codeine, tramadol, and tapentadol
15. Treatment with any MOR including codeine, tramadol, and tapentadol within a period of 1 month before Visit 1.
16. History of problematic use of opioids, e.g., dependency, as judged by the Investigator.
17. Concurrent treatment with medicines that are: a. Substrates of CYP2C8 (e.g., amiodarone, repaglinide, montelukast, paclitaxel, pioglitazone, treprostinil) b. Sensitive substrates of CYP3A4 and/or with a low therapeutic index (e.g., cyclosporine, eplerenone, felodipine, lercanidipine, midazolam, quetiapine, simvastatin, sildenafil, tacrolimus) c. Strong inhibitors of CYP2D6 (e.g., bupropion, fluoxetine, paroxetine, quinidine) d. Strong inhibitors of CYP3A4 (e.g., ceritinib, clarithromycin, cobicistat, idelalisib, ketoconazole, posaconazole, ritonavir, voriconazole) e. Strong inducers of CYP3A4 (e.g., apalutamide, carbamazepine, dabrafenib, enzalutamide, ivacaftor, lumacaftor, phenytoin, primidone, rifampin, St. John’s wort)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. • Safety parameters to be recorded throughout the trial: o Laboratory values, vital signs, physical examination including neurological examination, and electrocardiogram (ECG), evaluated with regard to change from Baseline where appropriate and with regard to abnormalities found and clinical significance
2. • Safety parameters to be recorded throughout the trial: Adverse events (AEs), assessed with regard to intensity, seriousness, and causality

Secondary endpoints 9

1. • Pain assessments: Change of “Average Pain” Intensity (last 12 hours) rated on Numerical Rating Scale (NRS; 0-10, twice daily) from 5-days Baseline to the last 5 days of each treatment period
2. • Pain assessments: Change of Touch-Evoked Pain Intensity (“Pain caused by touch/contact” with the painful skin area during the night/day) rated on NRS (0-10) from 5-days Baseline to the last 5 days of each treatment period
3. • Pain assessments: Change from Baseline in Pain Interference with sleep, daily activities, and mood, respectively, during the last 24 hours, rated on NRS (0-10)
4. • Pain assessments: Change in Neuropathic Pain Symptom Inventory (NPSI) total score and its 5 subdimensions during each treatment period
5. • Pain assessments: Pain relief experienced during each treatment period, rated on a Pain Relief Scale (none, a little, some, a lot, complete)
6. • Pain assessments: The change in consumption of rescue medication (paracetamol) from 5-days Baseline to the last 5 days of each treatment period
7. Change from Baseline to the last day of each treatment period of the intensity (NRS, 0-10) of dynamic mechanical allodynia, as evoked by standardised brush strokes in the skin area of maximal pain
8. Change from Baseline to the last day of each treatment period in the area of dynamic mechanical allodynia, using strokes with a standardised brush
9. Descriptive statistics of plasma concentrations of PN6047 HCl in participants receiving active treatment, at -15 min (±14 min, pre-dose), +30 min, +60 min, +90 min, and +4 h after dose on Days 7, 20, 35, and 48. On Day 29, only a pre-dose sample will be collected

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pharmnovo AB

Sponsor organisation

Pharmnovo AB

Address

Scheeletorget 1

City

Lund

Postcode

223 63

Country

Sweden

Scientific contact point

Organisation

Pharmnovo AB

Contact name

Scientific Contact Point

Public contact point

Organisation

Pharmnovo AB

Contact name

Public contact point

Third parties 2

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications