| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Postherpetic Neuralgia (PHN) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Postherpatic neuralgia: pain present for more than 3 months after the healing of the herpes zoster skin rash (shingles) |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 15.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10034911 |
| E.1.2 | Term | PHN |
| E.1.2 | System Organ Class | 100000004852 |
|
| 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 |
The primary objective is to obtain pilot prospective data to explore whether sensory symptom cluster analysis is useful for predicting treatment response in PHN.
- Phenotype PHN subjects entering study with sensory symptom clustering using the PainPREDICT, PainDETECT and NPSI questionnaires, “baseline pain interference with sleep”, Patient Health Questionnaire 8 (PHQ-8), Generalized Anxiety Disorder 7-item (GAD-7), as well as Pain Catastrophizing Scale (PCS) questionnaire.
- Find “responders” and “non-responders” to treatment (pregabalin).
- Compare distribution of phenotypes within “responder” and “non-responder” groups. |
|
| E.2.2 | Secondary objectives of the trial |
| The secondary objective is to evaluate the safety and tolerability of pregabalin in this population and to evaluate the efficacy of pregabalin to relieve pain and to improve global assessment, anxiety and depression, functional status, and sleep. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and self complete all questionnaires in addition to all other study procedures.
3. Men or women of any race or ethnicity who are at least 18 years of age.
4. Male and female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 30 days after the last dose of assigned treatment. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active. Women must be nonpregnant and nonlactating; all women must have a confirmed negative serum pregnancy test at baseline.
5. Female subjects who are not of childbearing potential (ie, meet at least one of the following criteria):
• Have undergone hysterectomy or bilateral oophorectomy;
• Have medically confirmed ovarian failure; or
• Are medically confirmed to be post-menopausal (eg, cessation of regular menses for ≥12-months with no alternative pathological or physiological cause) or serum FSH level, confirmed via a single repeat if deemed necessary, within the central laboratory’s reference range for postmenopausal state.
6. Subjects must have pain present for more than 3 months after the healing of the herpes zoster skin rash.
7. At screening (V1) and baseline (V2), subjects must have a score of ≥4 on the Numeric Rating Scale for Pain (1-week recall period).
8. At baseline (V2), at least 4 pain diaries must be completed satisfactorily within the last 7 days and the average pain score must be ≥4.
|
|
| E.4 | Principal exclusion criteria |
1. Subjects having other severe pain that may confound assessment or self-evaluation of the pain due to PHN.
2. Neurolytic or neurosurgical therapy for PHN.
3. Skin conditions in the affected dermatome that could alter sensation.
4. Have failed alpha-2-delta (ie, pregabalin, gabapentin) treatment due to lack of efficacy or have intolerance to pregabalin/gabapentin or any pregabalin/gabapentin ingredient, or participated in a pregabalin clinical trial. If the subject has taken pregabalin/gabapentin and discontinued for reason other than lack of efficacy or intolerance, then they will be eligible. However use within the last 6 months (prior to V1) is not permitted.
5. Use of prohibited medications in the absence of appropriate washout periods (see Section 5.5 and 5.6 of the protocol).
6. Subjects with any clinically unstable, cardiovascular, hematological, autoimmune, endocrine, renal, hepatic, retinal or gastrointestinal disease. Subjects that are HIV positive, with no AIDS and no sign of HIV related neuropathy is acceptable.
7. Any subject considered at risk of suicide or self harm based on investigator judgment and/or the details of a risk assessment (see Section 7.3.5.3 of the protocol).
8. Estimated creatinine clearance (CLcr) ≤60 mL/min (using Cockcroft-Gault equation). Subjects who have an estimated CLcr ≤60 mL/min by this screening method may have their CLcr measured, at the investigator’s discretion, with a 24-hour urine collection performed at the central laboratory. If this 24-hour urine CLcr is >60 mL/min, the subject is not excluded.
9. Participation in any clinical trial within the 30 days prior to screening and/or during study participation.
10. Screening electrocardiogram (ECG) with any clinically significant abnormality.
11. Have had a malignancy other than basal cell carcinoma or carcinoma in situ of the cervix within the past 5 years.
12. Subjects with difficulties swallowing capsules or unable to tolerate oral medication.
13. Platelet count <100x109/L; white blood cell (WBC) count <2.5x109/L; neutrophil count <1.5x109/L.
14. Alcohol or substance abuse or dependence within the previous year per investigator judgment.
15. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
16. Pregnant females; breastfeeding females; males and females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for at least 30 days after last dose of investigational product.
17. Subjects who are investigational site staff members or relatives of those site staff members or subjects who are Pfizer employees directly involved in the conduct of the trial. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The change in the daily pain diary (Numerical Rating Scale, NRS) mean pain score at the end of the study (Week 6) compared with baseline. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Daily pain diary (daily), PainDETECT and PainPREDICT questionnaires (screening and days 1, 8, 15, 22, 29,43,& 50), NPSI (screening and days 1, 8, 15, 22, 29,43,& 50) |
|
| E.5.2 | Secondary end point(s) |
Proportion of subjects within each phenotype groups as determined by sensory symptom clustering using the PainPREDICT, PainDETECT and NPSI questionnaires, “baseline pain interference with sleep”, PHQ-8, GAD-7 as well as PCS questionnaire.
Proportions of subjects with ≥30% and ≥50% pain reduction based on daily pain diary.
Proportion of phenotypes within the 30% and 50% responder groups.
Pain numeric rating scale (NRS); 1 week recall period.
Neuropathic Pain Symptom Inventory (NPSI).
Patient Global Impression of Change (PGIC).
Short Form 12v2 Health Survey (SF-12v2).
The change in the daily sleep interference diary (Numerical Rating Scale, NRS) mean pain score at the end of the study (Week 6) compared with baseline.
Patient Health Questionnaire-8 (PHQ-8); GAD-7 questionnaire and
Brief Pain Inventory (BPI-sf). |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| PGIC (day 43), NRS-Pain (daily), sleep diary (daily), BPI-sf (day 1 & 43), PHQ-8 (screening and days 1 and 43), GAD-7 (screening and days 1 and 43), SF-12v2 (day 1 & 43), pain catastrophizing scale (day 1), Actiscore (1 week of screening and week 4). |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| 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 | No |
| E.8.2.3 | Other | No |
| 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 | 4 |
| 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 |
| Austria |
| France |
| Germany |
| Ireland |
| Mexico |
| Poland |
| South Africa |
| Spain |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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 | 1 |
| E.8.9.1 | In the Member State concerned months | 0 |
| 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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