E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008837 |
E.1.2 | Term | Chronic back pain |
E.1.2 | System Organ Class | 100000004859 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024891 |
E.1.2 | Term | Low back pain |
E.1.2 | System Organ Class | 100000004859 |
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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 determine whether the combination of sertraline and lamotrigine, when administered to subjects with low back pain is effective in pain relief. |
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E.2.2 | Secondary objectives of the trial |
To determine the safety profile of the combination compared with placebo by assessment of:
- Adverse Event (AEs) (including serious adverse events (SAEs)
- Laboratory values
- Electrocardiogram (ECG)
- Vital signs
- Body weight
- Physical examination |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written and signed patient information leaflet and informed consent form, obtained prior to starting any study related protocol-specific procedures.
2. Age between 18 and 75 years (inclusive both males and females).
3. 18 kg/m2 ≤ BMI ≤ 35 kg/m2 (and the minimal body weight is 40 kg)
4. Chronic low back pain (as primary painful condition) with presence of pain restricted to lower back or radiated to limb on most days for at least > 3 months.
5. The average spontaneous pain severity score is ≥4 measuring on an 11-point numeric pain intensity rating scale (BPI) by the patient during the period of 1 week prior to the screening and enrollment.
6. For women of childbearing potential, agreement to use highly effective non-hormonal form of contraception or two effective forms of hormonal/non-hormonal contraception by the patient and/or partner. Contraception use must continue for the duration of study treatment and for at least 2 weeks after the last dose of study treatment. |
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E.4 | Principal exclusion criteria |
1. Current uncontrolled hypertension (systolic > 160 mmHg and/or diastolic > 100 mmHg).
2. If QTc > 450 msec.
3. If patient had a surgery in the low back region within 3 months prior to screening.
4. If surgery is indicated for the chronic low back pain.
5. Other reasons of low back pain (abscess, tumor etc.) revealed by neuroimaging. Result of MRI scan performed 3 months prior to randomization is acceptable.
6. Current (i.e. within 3 month prior to screening) spinal fracture, Grade 3 or Grade 4 spondylolisthesis, abscess or acute pathological conditions in the low back/abdominal region.
7. Evidence of any other disease, metabolic or psychological dysfunction, physical examination findings or clinical laboratory finding giving reasonable suspicion of a disease or condition that can significantly interfere with the low back pain or generate unresolved considerations in its differential.
8. Significant cardiovascular history within the past 6 months up to screening defined as: myocardial infarction, coronary angioplasty or bypass graft(s), valvular disease or repair, unstable angina pectoris, transient ischemic attack, or cerebrovascular accident
9. Patients suffering from epilepsy.
10. History of depression or a current depressive episode. Patients with a score of ≥8 assessed by HADS are not eligible
11. Known hypersensitivity to sertraline or lamitrigine or any of the other ingredients of the study medications.
12. Known hypersensitivity to paracetamol.
13. Neurologic alteration of different origin which significantly affects the sensory or motoric functions (e.g. diabetic neuropathy).
14. Concurrent use of any type of medication having analgesic or muscle-relaxant effect, unless the medication is used regularly for at least 3 months in stable dose. Otherwise, any medication to relieve the pain (either systemic or local) or muscle spasms must have been discontinued for a period of at least 5 half-lives of the drug prior to the enrolment and are not allowed during the whole study period.
15. Concomitant use of monoamine-oxidase inhibitors, including the selective MAOI selegiline, the reversible MAOI moclobemide and reversible non-selective MAO inhibitor linezolid.
16. Concomitant use of pimozide, valproate, tramadol or any serotonergic drugs such as, sumatriptan.
17. Concomitant use of other analgesic methods, unless it is in a regular manner within 2 months prior to randomization (massage, physiotherapy, bath, etc.).
18. Inadequate organ functions, evidenced by laboratory results within 7 days prior to randomization.
19. History of drug or alcohol abuse within the past 2 years or current chronic or intermittent users of illicit drugs.
20. Lactating or pregnant women or women of child-bearing potential without appropriate contraceptive treatment.
21. Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequences of the study or to cooperate at the necessary level.
22. The patient, planned to be enrolled, is an employee of any involved study investigator or any involved institution including the study sponsor
23. Evidence of an uncooperative attitude.
24. Participation in another clinical trial with any investigational drug or device within 1 month or 5 x half-life of the investigational drug prior to study screening of this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in pain severity, assessed by using average pain ratings on an 11-point numerical rating scale from the baseline to the end of treatment (Brief Pain Inventory). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Assessment of Brief Pain Inventory scale will be performed during screening, baseline, week 9 (after treatment of maximal dose) and week 11 (FU1, after dose reduction phase). Patients will rate their pain. |
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E.5.2 | Secondary end point(s) |
1. Change in weekly mean pain scores of the nocturnal pain ratings (if the patient wakes up) from the baseline to the end of treatment (week 9) and to after reduction (week 11) measured by an 11-point numerical rating scale by the patients.
2. Change in Quality of life (EQ-5D) score assessment from baseline to the end of treatment (week 9) and to after reduction (week 11)
3. Change in Roland-Morris Disability Questionnaire (RMQ) from baseline to the end of treatment (week 9) and to after reduction (week 11)
4. Change in Athens Insomnia Scale from baseline to the end of treatment (week 9) and to after reduction (week 11)
5. Change in Hospital Anxiety and Depression Scale (HADS) between the following visits: screening, baseline, week 4, at the end of treatment (week 9) and after reduction (week 11)
6. Change in The Work Productivity and Activity Impairment (WPAI) from baseline to the end of treatment (week 9) and to after reduction (week 11)
7. Parameters of Brief Pain Inventory not covered in the primary endpoint from baseline to the end of treatment (week 9) and to after reduction (week 11)
8. Paracetamol intake during the treatment period |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Patient will complet a diary for noctural pain during the whole study and for paracetamol intake. All secondary endpoint will be assessed during baseline visit. At week 4 the Hospital Anxiety and Depression Scale (HADS) assessment will be performed. At week 9 and week 11 the following assessments will be performed:
- Change in Quality of life (EQ-5D)
- Change in Roland-Morris Disability Questionnaire (RMQ)
- Change in Athens Insomnia Scale
- Change in Hospital Anxiety and Depression Scale (HADS)
- Change in The Work Productivity and Activity Impairment (WPAI)
- Parameters of Brief Pain Inventory not covered in the primary endpoint |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
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 | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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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 |