E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Posttraumatic Neuralgia (neuropathic pain) |
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E.1.1.1 | Medical condition in easily understood language |
Posttraumatic neuropathic pain |
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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 | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054095 |
E.1.2 | Term | Neuropathic pain |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 investigate the analgesic efficacy of AZD2423 compared with placebo after 28 days of oral administration in patients with PTN. |
|
E.2.2 | Secondary objectives of the trial |
1. To investigate the responder rate of patients receiving AZD2423 compared to
placebo in patients with PTN.
2. To investigate the analgesic efficacy of AZD2423 on different components of pain
compared to placebo in patients with PTN.
3. To investigate the effect of AZD2423 on different functional consequences of pain
compared to placebo in patients with PTN.
4. To investigate the PK of AZD2423 in patients with PTN.
5. To investigate the safety and tolerability of AZD2423 in patients with PTN. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provision of informed consent prior to any study specific procedures
2. Male, or female of non-child bearing potential (18-80 years, inclusive). Only women of non-child bearing potential are included in the study, ie, women who are permanently or surgically sterilised or post menopasual:
− Women will be considered post menopausal if they are amenorrheic for 12 months without an alternative medical cause.
The following age-specific requirements apply:
− Women under 50 years old will be considered post menopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range.
− Women over 50 years of age will be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments.
Permanent sterilization includes hysterectomy and/or bilateral oopherectomy and/or bilateral salpingectomy but excludes bilateral tubal occlusion.
3. Neuropathic pain due to peripheral nerve injury caused by trauma or surgery.
Duration of neuropathic pain must be at least three months and at most 5 years.
Complex Regional Pain Syndrome (CRPS) type II is accepted provided that pain is due to a defined nerve injury. Nerve injuries at plexus or root level are excluded.
4. Pain intensity (7 days recall) of 4-9 (inclusive) on NRS - Average Pain (0-10) is required for enrolment. At randomisation a 5-day mean baseline NRS - Average Pain intensity (12 h recall twice daily, morning and evening) of 4-9 (inclusive) is required. The patient is also required to complete at least 4 out of 5 morning and evening baseline NRS - Average Pain assessments Day –5 to Day –1 to be eligible.
5. Be able to understand and comply with the requirements of the study as judged by the investigator.
For inclusion in the genetic research, patients must fulfil the following criterion:
6. Provision of informed consent for genetic research. If a patient declines to participate in the genetic research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in this CSP, so long as they consent. |
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E.4 | Principal exclusion criteria |
1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
2. Previous enrolment or randomisation in the present study.
3. Participation in another clinical study with an IP during the last 30 days prior to enrolment.
4. Other pain that may confound assessment of neuropathic pain, as judged by the
investigator.
5. Central neuropathic pain conditions (caused by CNS injury/disease, eg, stroke, multiple sclerosis or spinal cord injury).
6. Any prior treatment of neuropathic pain with intrathecal pump or spinal cord stimulator.
7. History of treatment failure with ≥3 adequate trials of medications used to treat neuropathic pain, as judged by the investigator.
8. Use of any prohibited medication (see Table 4) at Visit 2.
9. History of any unstable medical disease (eg,, cardiovascular, renal insufficiency, hepatic insufficiency) which may interfere with the objectives of the study or with the safety of the subject, as judged by the investigator.
10. History of gastric ulcer or haemorrhage
11. History of significant psychiatric disease/disorder that could preclude reliable participation in the study, as judged by the investigator.
− Patients with a diagnosis of depression who are in remission for at least 12 weeks before enrolment with or without stable SSRI treatment are allowed in the study.
12. Patient with a cognitive disorder which could impair cooperation with study procedures, as judged by the investigator.
13. Clinically significant illness within 2 weeks before the administration of the IP as judged by the investigator.
14. Known malignancy within the past 5 years (with the exception of successfully treated basal cell carcinoma).
15. Malabsorption, gastrointestinal disorder or surgery leading to impaired drug absorption.
16. Donation of plasma from 2 weeks before Visit 1 (enrolment visit) or donation of blood from 3 months before Visit 1.
17. Abnormal vital signs, laboratory test value or ECG of clinical significance, as judged by the investigator.
− QTcF>450 ms or <340 ms, or a family history of long QT syndrome.
− Calculated Creatinine clearance ≤50 mL/min assessed by the Cockroft-Gault method.
− ALT or AST >1.5xULN
− Bilirubin > 1xULN
18. Positive Tuberculosis screening (i.e. chest x-ray and QuantiFERON® – TB Gold according to local requirements) as judged by investigator.
19. Immunisation with live vaccine within the previous 3 months, for other vaccines within the past 30 days.
20. History of latent, chronic, or recurrent infections (eg, tuberculosis, recurrent sinusitis, genital herpes, urinary tract infections) or at risk of infection (surgery,
trauma or significant infection, history of skin abscesses within 90 days prior to Visit 1).
21. Women with a positive pregnancy test on enrolment or before randomisation or lactating women.
22. History of alcohol or drug abuse within 2 years of entering the study.
23. Contraindication to ibuprofen/NSAIDs, such as ulcer and history of hypersensitivity reactions (eg, asthma, rhinitis or urticaria).
24. History of or positive test of human immunodeficiency virus (HIV) or hepatitis B or C.
25. Positive urine toxicology results for drugs of abuse including cannabis, cocaine, ecstacy, heroin/morphine, amphetamine and phenocyclidine (PCP). Visit 1 urine
toxicology results indicating opiate or other prescribed analgesic (including benzodiazepines) use in patients who had been receiving the medications for therapeutic reasons are permitted. However, patients who test positive for opiates or other excluded medications at Visit 2 (after the appropriate washout) are excluded.
In addition, any of the following is regarded as a criterion for exclusion from the genetic research:
1. Previous allogeneic bone marrow transplant.
2. Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in mean NRS Average Pain Score |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline (Day –5 to Day –1) to Day 24 to Day 28. |
|
E.5.2 | Secondary end point(s) |
1. Change from baseline in Numeric Rating Scale Pain Interference on Sleep and Activity score
2. To investigate the safety and tolerability of AZD2423 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Baseline (Day –5 to Day –1) to Day 24 to Day 28.
2. Weekly
|
|
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability and response rate |
|
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 | 3 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 |
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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
|
The last visit of the last patient undergoing the study. |
|
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 | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |