| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10044127 |
| E.1.2 | Term | Tourette's syndrome |
|
| 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 aim of this clinical trial is to demonstrate the efficacy and safety of one or more daily doses of pramipexole (PPX) compared to placebo for the treatment of tics in patients 6-17 years of age diagnosed with TS according to DSM-IV criteria. |
|
| E.2.2 | Secondary objectives of the trial |
Secondary endpoints relating to efficacy to be evaluated at the end of treatment (Week 8) visit include the following:
• Change from baseline in the YGTSS total score
• Change from baseline in CGI-S
• CGI-I response (“much” or “very much improved”)
• PGI-I response (“much” or “very much better”) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Main criteria for inclusion: Male or female patients 6-17 years of age diagnosed with Tourette Syndrome according to DSM-IV criteria and a Total Tic Score (TTS) of ≥22 derived from the Yale Global Tic Severity Scale (YGTSS).
1. Male or female patients 6 to 17 years of age.
2. Written informed consent provided by the patient’s parent (or legal guardian) and
assent provided by the patient at the time of ICF signature. All informed
consent/assent forms should be consistent with ICH/GCP and Local Institutional
Review Board (IRB) requirements and must be obtained prior to any study procedures being performed.
3. Ability and willingness to comply with study treatment regimen and to attend study
assessments. Subjects must be willing and able to swallow tablets.
4. Diagnosed with TS as per the below DSM-IV criteria and with a score ≥22 on the
Total Tic Score (TTS) of the YGTSS at screening or baseline:
• Both multiple motor and one or more vocal tics have been present at some time
during the illness, although not necessarily concurrently. (A tic is a sudden, rapid,
recurrent, non-rhythmic, stereotyped motor movement or vocalization.)
• The tics occur many times a day (usually in bouts) nearly every day or
intermittently throughout a period of more than 1 year, and during this period there
was never a tic-free period of more than 3 consecutive months.
• The onset is before age 18 years.
• The disturbance is not due to the direct physiological effects of a substance
(e.g., stimulants) or a general medical condition (e.g., Huntington’s disease or
post-viral encephalitis).
• The disturbance causes marked distress or significant impairment in social,
occupational, or other important areas of functioning.
5. Diagnosis of TS must be confirmed via administration of the Kiddie-Schedule for
Affective Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL).
6. Females of childbearing potential must have a negative serum β-hCG pregnancy test at the Visit 1 unless surgically sterile.
7. Females of childbearing potential must be using a medically accepted contraceptive
method and must agree to avoid pregnancy during the study. Acceptable methods of
birth control are limited to: Intra-Uterine Device (IUD); oral, implantable or injectable
contraceptives and estrogen patch; double barrier method (spermacide + diaphragm); or abstinence at the discretion of the investigator.
8. Either a de novo patient not on current treatment for TS, or a patient who has been diagnosed with TS but who the investigator feels has not been adequately managed using current therapy, or has failed current therapy, whereby the patient may benefit in the use of pramipexole and, if on current therapy, can be safely discontinued from such therapy prior to enrolment into this study.
9. Having a body weight ≥20 kg. |
|
| E.4 | Principal exclusion criteria |
1. Breastfeeding females.
2. Clinically significant renal disease or serum creatinine out of this
range: 0.3-1.0 mg/dL for patients aged 3-12 years and 0.5-1.4 mg/dL for patients aged 13+ years.
3. Any of the following lab results at screening:
• Hemoglobin (Hgb) below lower limit of normal (LLN) which is determined to be
clinically significant.
• Basal thyroid stimulating hormone (TSH), triiodothyronine (T3) or thyroxine (T4)
clinically significant (at the investigator’s discretion) out of normal range at
screening (if not caused by substitution therapy according the investigator’s
opinion).
• Patients with any clinically significant abnormalities in laboratory parameters at
screening at the investigator’s discretion.
4. Other clinically significant metabolic-endocrine, hematological, gastrointestinal
disease, pulmonary disease (such as severe asthma) in the opinion of the investigator would preclude the patient from participating in this study. Controlled asthma is exempt from this criterion.
5. History or current presence of schizophrenia or any psychotic disorder.
6. History or current presence of any psychiatric disorder (except for TS, ADHD or
OCD) that is of sufficient severity to require prescription medical therapy.
7. Pharmacological, herbal and/or alternative treatments for TS, ADHD and/or OCD are not allowed during the trial. See Section 4.2.2 for complete details and washout
information.
8. Patients receiving psychological, cognitive and/or behavioral treatments for TS, OCD and/or ADHD are excluded unless they started the treatment at least 3 months prior to randomisation and no changes in treatment are planned for the duration of this study.
9. History or presence of clinical signs of epilepsy or seizures other than fever-related
seizures in early childhood.
10. History or presence of clinical signs of any malignant neoplasm including suspicious undiagnosed skin lesion (which may be melanoma), melanoma, or a history of melanoma. Albinotic patients.
11. Patients who meet criteria for Restless Legs Syndrome and/or Periodic Limb
Movement disorder.
12. Allergic response to pramipexole or the inactive ingredients in its tablet formulation.
13. Had previous treatment with dopamine agonists other than pramipexole within
14 days prior to baseline visit.
14. Patients who report withdrawal symptoms of any medication at screening or at the baseline visit.
15. K-BIT2 IQ score less than 70 at screening. For patients in Canada and United States whose primary language is English, this score is derived from the composite score of verbal and non-verbal sections of the evaluation. For all other patients whose primary language is not English (in Canada, the United States or other countries) the score is derived exclusively from the non-verbal section of the evaluation.
16. A total score greater than 15 at the screening visit on the CY-BOCS.
17. Retinal abnormalities.
18. History of alcohol abuse, substance abuse or any prescribed or over-the-counter
medication usage in a manner which, in the opinion of the Investigator, indicates
abuse.
19. Any other conditions that in the opinion of the investigator would interfere with the evaluation of the results or constitute a health hazard for the patient.
20. Concurrent participation in another clinical trial using any investigational drug.
21. Patients previously randomised in Study 248.644. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline to end of treatment visit (Week 8) in the Total Tic Score (TTS) of the Yale Global Tic Severity Scale (YGTSS) |
|
| 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 | 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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.8.1.7.1 | Other trial design description |
|
| 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.8.3 |
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 | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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 |
|
| 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
|
| End of the trial will be 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 | |
| E.8.9.1 | In the Member State concerned months | 16 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 16 |
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