| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| A painful condition that affects the nerve fibers and skin. It is a complication of shingles, and shingles is a complication of chicken pox. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10036376 |
| E.1.2 | Term | Post herpetic neuralgia |
| E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the efficacy of LX9211 in reducing pain related to postherpetic neuralgia (PHN) |
|
| E.2.2 | Secondary objectives of the trial |
| To assess other effects and patient reported outcomes of LX9211 versus placebo during and following the Week 6 double-blind Treatment Period |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Patient has given written informed consent to participate in the study in accordance with local regulations
2. Adult male or female patients ≥18 years of age at the Screening Visit:
a. Females of childbearing potential must have a negative serum or urine pregnancy test prior to the start of study drug. In the case of positive urine pregnancy testing, a negative serum sample for pregnancy testing, to confirm that the patient is not pregnant, must be obtained prior to start of study. They must also agree to use birth control methods which may be considered as highly effective, i.e. methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include:
• oral, intravaginal or transdermal combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation
• oral, injectable or implantable progestogen-only hormonal contraception associated with inhibition of ovulation
• intrauterine device
• intrauterine hormone-releasing system
• bilateral tubal occlusion
• vasectomized partner
• sexual abstinence
b. Nonsterile male patients with sexual partners of childbearing potential must agree to use adequate methods of contraception from Baseline through the Week 11 Visit
3. Presence of PHN pain that is present for ≥3 months after healing of herpes zoster skin rash affecting a single dermatome (Patients with more than 1 involved dermatome may also be included, provided the affected dermatomes are contiguous)
4. Moderate to severe pain as confirmed by average pain score using scores recorded in the pain diary in the 14 days prior to randomization (Run-in Period)
5. At least 80% compliance with dosing during the 2-week Run-in Period, and 70% compliance with completion of the daily diary during the second week of the Run-in Period
6. Willing to adhere to the prohibitions and restrictions specified in the protocol |
|
| E.4 | Principal exclusion criteria |
1. Presence of other painful conditions that may confound assessment or self-evaluation of PHN:
a. Patient should not have any other neurological disorder or conditions that can cause symptoms that may mimic peripheral neuropathy or that might confound assessment of PHN pain.
b. Other causes of diffuse painful peripheral neuropathy such as: paraproteinemia, untreated hypothyroidism (previously treated hypothyroidism not excluded if treated and euthyroid for ≥6 months), vitamin B12 deficiency, neurologically-evident vasculitis, malignancy, amyloidosis, renal insufficiency, connective tissue disease (eg, Sjogren's, systemic lupus erythematosus), porphyria, complex regional pain syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, alcoholism, HIV, hepatitis, uremia, syphilis, myeloma, or other systemic disease associated with a secondary painful neuropathy should be excluded.
c. Patient should not have had any exposure to drugs/toxic environmental agents known to cause neuropathy
2. Over the past year, met Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for a major depressive episode, any active, significant psychiatric disorders (eg, neurocognitive disorder, anxiety disorder, psychosis, bipolar disorder), or a history of clinically significant drug or alcohol use disorder that would, in the Investigator's opinion, interfere with the assessment and evaluation of pain during the study
3. Mood and anxiety disorder scores defined by Hospital Anxiety and Depression Scale (HADS) ≥13
4. Suspected or likely diagnosis of trigeminal neuralgia
5. Use of opioid medications for management of PHN within the 2 months prior to the Screening Visit. Note: Brief use (<1 week) of opioid medication for management of non-PHN acute pain (eg, tooth extraction/acute injury) ≥2 months prior to the Screening Visit is permitted.
6. Use of NSAIDs for the specific treatment of PHN pain.
7. Use of more than 1 permitted concomitant medications for the treatment of PHN. Permitted medications include gabapentin, pregabalin, and tricyclic antidepressant medications. Note: Patients may washout additional PHN medications ≥1 month prior to the Screening Visit to reach the 1 permitted medication
8. For non-opioid medications patient uses and is unwilling/unable to discontinue use of prohibited medications and therapies, (eg, benzodiazepines, dextromethorphan, herbal medications, mexiletine HCl, adenosine, topical analgesics including lidocaine and capsaicin), applied to the same area of the body affected by PHN pain, nerve blocks, acupuncture, or other medications indicated for neuropathic pain. A patient using any of these interventions for neuropathic pain must discontinue the medication ≥1 month prior to starting the Screening Period and for the duration of the study. Note: This exclusion criterion does not include analgesics that are not specifically prescribed for treatment of neuropathic pain (eg, nonsteroidal anti-inflammatory drugs [NSAIDs] and aspirin). In addition, patients who are prescribed antidepressants for a mental health disorder are eligible to participate as long as they do not meet Exclusion Criteria 2-3.
9. A positive urine drug test for drugs of abuse including cannabinoids. Note: Cannabidiol (CBD), if used for mood or sleep, is acceptable. If used for PHN it would be allowed if it is the only concomitant medication being taken for PHN. If not the only medication being taken for PHN, it should be withdrawn ≥1 month prior to Screening
10. Patient has hepatic impairment at Screening, defined as any of the following: aspartate aminotransferase (AST) >2X upper limit of the normal reference range (ULN), alanine aminotransferase (ALT) >2X ULN, serum total bilirubin (TB) >2X ULN. Note: If it is the opinion of the Investigator and the Medical Monitor that an increase in bilirubin is due to Gilbert’s syndrome, then the patient may participate.
11. Patient has abnormal kidney function test (estimated glomerular filtration rate [eGFR] <60 mL/min as calculated using the Cockcroft-Gault equation) at Screening or renal dysfunction requiring hemodialysis
12. Patient has any of the following medical conditions or disorders: epilepsy or seizure disorder requiring treatment with antiepileptic drugs
13. Presence of clinically significant physical examination (PE) findings other than PHN, or laboratory or ECG findings that in the opinion of the Investigator, Medical Monitor, and/or the Sponsor, may interfere with any aspect of study conduct or interpretation of results including:
a. any clinically significant abnormal heart rate or rhythm
b. other ECG abnormalities that are clinically relevant
c. BP >160/100 mm Hg or <90/50 mm Hg
d. presence of risk factors for torsade de points (eg, family history of long QT syndrome; personal history of NYHA class III/IV heart failure or structural heart disease)
Refer to protocol for further criteria |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The change from Baseline (Week 2 of the Run-in Period) to Week 6 in Average Daily Pain Score (ADPS), based on Question 5 of the Zoster Brief Pain Inventory (ZBPI), the 11-point numerical rating scale (0 [No Pain] to 10 [Pain as bad as you can imagine]) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
• Change from Baseline to Week 6 in pain interfering with sleep based on Question 9F of the ZBPI “Indicate the one number that describes how, in the past 24-hours shingles pain has interfered with your: Sleep (0 [Does not interfere] to 10 [Completely interferes])”
• Proportion of patients with ≥30% reduction in pain intensity in ADPS based on Question 5 of the ZBPI from Baseline to Week 6
• Proportion of patients with ≥50% reduction in pain intensity in ADPS based on Question 5 of ZBPI from Baseline to Week 6
• Change from Baseline to Week 6 in interference in General Activity, Mood, Walking Ability, Normal Work (includes both outside the home and housework), Relations with other people, Sleep, and Enjoyment of Life interference based on the Questions 9A-G of the ZBPI
• Proportion of patients discontinuing treatment due to lack of efficacy defined as increase in ADPS from Baseline of ≥30% based on Question 5 of the ZBPI
• Patient Global Impression of Change (PGIC) at Week 6
• Time to loss of efficacy from Week 6 to Week 11 among patients achieving ≥30% reduction in pain intensity in ADPS based on Question 5 of the ZBPI. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Czechia |
| Poland |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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