| 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 |
| generalized wide-spread musculoskeletal pain |
|
| 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 | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10048439 |
| E.1.2 | Term | Fibromyalgia |
| E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue 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 safety and efficacy of pregabalin (75-450 mg/day) compared with
placebo in an adolescent fibromyalgia population. |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the pharmacokinetics of pregabalin in an adolescent fibromyalgia population.
Other objective:
Collection of data to help characterise the adolescent fibromyalgia population and facilitate future clinical studies.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female of any race and 12-17 years of age, inclusive.
2. Subjects and one parent (or legal guardian) must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Study medication will not be dispensed to a minor; a parent/guardia/caregiver must be available to pick up study medication for study patient at Visit 2 (Randomization), Visit 6, Visit 8, Visit 9 and Visit 10. Dose adjustments (except dose reductions required for safety reasons) will not be made without parent/guardian/caregiver agreement (refer to Section 5.3.2 for detailed instructions).
3. Subjects and one parent (or legal guardian) must have personally signed and dated a legally effective written informed assent and consent indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study, prior to admission to the study.
4. At screening (V1), subjects must meet the Yunus and Masi criteria (1985)6 for fibromyalgia - generalized musculoskeletal aching at 3 or more sites for 3 or more months, 5 or more tender points, and 3 or more of the following 10 minor criteria should be present:
Chronic anxiety or tension
• Fatigue
• Nonrestorative sleep, defined as waking from sleep feeling tired
• Chronic headaches
• Irritable Bowel Syndrome, defines as altered bowel habits associated with abdominal pain or discomfort
• Subjective soft tissue swelling
• Numbness
• Pain modulation by physical activities
• Pain modulation by weather factors
• Pain modulation by anxiety or stress
If 5 of the above minor criteria are present, 4 tender points will satisfy the criteria.
5. At screening (V1) and randomization (V2), patients must have a score of at least 4 (greater than or equal to 4) on the Weekly Pain Numeric Rating Scale (Pain-NRS).
6. At randomization (V2), at least 4 pain diaries must be completed satisfactorily within the preceding 7 days and the average daily pain score must be at least 4 (greater than or equal to 4). |
|
| E.4 | Principal exclusion criteria |
1. Subjects with pain due to other conditions that may confound assessments or self-evaluation of the pain associated with fibromyalgia.
2. Subjects with systemic inflammatory musculoskeletal disorders or rheumatic diseases other than fibromyalgia, serious active infections, or untreated endocrine disorders. Patients with a history of Juvenile Rheumatoid Arthritis (JRA) now in remission and no longer being treated, with no planned initiation of treatment may be enrolled.
3. Previous participation in clinical trial with pregabalin, failed pregabalin treatment due to lack of efficacy, have intolerance to pregabalin or any pregabalin ingredient, or taking pregabalin currently or within the last 30 days for any condition.
4. Subjects with unstable depressive disorders, unstable Attention Deficit Hyperactivity Disorder (ADHD), or any history of bipolar (mania or hypomania) or psychotic disorder, as assessed by structured interview using the Mini International Neuropsychiatric Interview (MINI-KID) assessment (refer to Section 7.1.2) are excluded. Subjects with any other clinically significant or unstable psychiatric disorder that in the judgment of the investigator would make the patient inappropriate for entry into this trial are excluded. For subjects with a current DSM diagnosis of a depressive disorder, anxiety disorder, or ADHD (or who meet criteria for one of these conditions based upon the MINI-KID), the following criteria must be met to be eligible:
Subjects with an anxiety disorder or depressive disorder: Must have stable symptoms that do not require pharmacologic treatment, OR be treated for these symptoms (refer to Section 5.5.2) for at least 3 months, with the last 2 months prior to Visit 1 at a stable dose and not considering a further increase in dose at study entry.
Subjects with ADHD: Must have stable symptoms that do not require pharmacologic treatment, OR must be on a pharmacologic treatment for ADHD for at least 3 months prior to Screening (V1), with the 2 months prior to V1 at a stable dose (refer to Section 5.5.2) and unlikely to require a dose adjustment during the study.
Any non-pharmacological treatments must be stable as described in Section 4.4.
5. Any subject at risk of suicide or self harm based on investigator judgment and/or details of a risk assessment by a qualified mental health professional, as specified in Section 7.4.2.3.
6. Subjects with serious hepatic, respiratory, neurologic (epilepsy, multiple sclerosis), cardiovascular, hematologic or immunologic illnesses, or any other severe acute or chronic medical or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results in the judgment of the investigator.
7. Pregnant or nursing females; patients who are unwilling or unable to use an acceptable method of contraception (or abstinence), as outlined in the Life Style Guidelines, from screening (V1) until completion of follow-up procedures. Females must have a negative serum pregnancy at screening (V1) prior to randomization.
8. Subjects with active malignancy of any type or any history of a malignancy.
9. Subjects who are immunocompromised.
10. Subjects with a history of illicit drug or alcohol abuse within the last 2 years. A urine drug screen for non-therapeutic drugs will be performed at screening; subjects testing positive will not be randomized. Subjects testing positive for opioid use may have a repeat urine drug screen at the discretion of the investigator, and may be randomized if the repeat test is negative.
11. CLcr <=80 mL/min (estimated from serum creatinine using Cockroft-Gault equation, Section 7.4.1).
12. Platelet count <100x 109/L; white blood cell (WBC) count <2.5 x 109/L; neutrophil count <1.5 x 109/L.
13. C-reactive protein <=2.00 mg/L.
14. Rheumatoid factor (RF>80 IU/mL).
15. Abnormal (clinically relevant) 12-lead electrocardiogram (ECG); must be reviewed/confirmed by investigator.
16. Subjects taking any other investigational drugs within 30 days prior to screening (V1).
17. Subjects with active gastrointestinal disease (GI) including any GI surgery that in the opinion of the investigator would interfere with the absorption of study medication.
18. Subjects with difficulty swallowing capsules or unable to tolerate oral medications.
19. Unwilling or unable to comply with the Life Style Guidelines (Section 4.4).
20. Use of certain medications for pain, sleep or for the treatment of fibromyalgia are prohibited, as detailed in Section 5.5.1. Certain antidepressants, sleep medications, and medications for the treatment of ADHD are allowable under specific conditions (refer to Section 5.5.2). Non-steroidal anti-inflammatory drugs (NSAIDS) and selective COX-2 inhibitors are permitted. Acetaminophen (up to 3 g/day) as rescue medication is permitted. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Endpoint mean pain score from the daily pain diary, defined as the mean of the last 7 pain diary entries prior to Visit 10 in the study while the patient is on study medication. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Mean pain score from daily pain diary (mean of the last 7 pain diary entries) prior to Visit 10 or Early Term |
|
| E.5.2 | Secondary end point(s) |
- Endpoint mean sleep quality score from the daily sleep diary, defined as the mean of the last 7 diary entries prior to Visit 10 in the study while the patient is on study medication.
- Weekly Pain Numeric Rating Scale (Pain-NRS) at Termination Visit (V10/Early Termination).
- Patient Global Impression of Change at Termination Visit (V10/Early Termination). |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Weekly pain numeric rating score at Visit 10; mean (last 7 entries) sleep quality score at Visit 10; patient global impression of change at Visit 10 |
|
| 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 | 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) | 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 | 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| 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 |
| India |
| Taiwan |
| 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 | 2 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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