| 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 | 8.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061536 |
| E.1.2 | Term | Parkinson's disease |
|
| 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 of the study is to assess the preliminary safety and tolerability of single and multiple oral doses of BIIB014 when administered as adjunct therapy in subjects with moderate to late-stage PD who are also receiving L-DOPA. |
|
| E.2.2 | Secondary objectives of the trial |
1. To explore the PK of BIIB014 and its N-acetyl metabilite when administered as adjunct therapy to subjects with moderate to late-stage PD.
2. To explore the activity of BIIB014 when administered as adjunct therapy to subjects with moderate to late-stage PD. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Unless otherwise specified, to be eligible to participate in this study, candidates must meet the following eligibility criteria at the time of the Day 1 Visit:
1. Must give written informed consent and any authorizations required by local law.
2. Must be at least 30 years old at the time of informed consent.
3. Must carry a diagnosis of idiopathic PD according to the UK Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria.
4. Must be on a stable dose of L-DOPA in conjunction with a dopa-decarboxylase inhibitor (e.g., L-DOPA/carbidopa or L-DOPA/benserazide) administered at least 3 times per day for at least 4 weeks prior to the Day 1 Visit. Subjects must be willing and able to continue on this L-DOPA regimen throughout their participation in the study.
5. Subjects taking dopaminergic therapies allowed by the protocol must have been on a stable dose for at least 4 weeks prior to the Day 1 Visit and must be willing and able to continue their regimen throughout their participation in the study.
6. Except for L-DOPA and allowed dopaminergic therapies, subjects must be willing and able to refrain from any other PD medication not permitted by the protocol throughout their participation in the study.
7. Must be Hoehn & Yahr Stage II-IV inclusive when OFF.
8. Subjects enrolled into Part B must have definite end of L-DOPA dose wearing OFF (at least 2 hours of OFF time per waking day confirmed by the subject’s Hauser Patient Diary).
9. Subjects enrolled into Part B must demonstrate the ability to keep accurate Hauser Patient Diaries of PD activity prior to randomization: at least 80% concordance between subject and Investigator/Trainer diary ratings (comparing OFF time, ON time without dyskinesias, and ON time with dyskinesias [troublesome or non-troublesome]) must be achieved during a diary training session. Subjects must have at least one transition from OFF to ON or from ON to OFF during the training session(s). Subjects must be willing and able to complete adequate Hauser Patient Diaries throughout the study period.
10. Subjects enrolled into Part B must provide a valid Hauser Patient Diary, defined as containing no more than 4 missing or duplicative entries per day for Days –3, -2, and –1, at the Day 1 Visit.
11. Male and female subjects of child-bearing potential must be willing to practice effective birth control for the duration of the study. Female subjects must be: (1) postmenopausal for at least 12 months, (2) surgically sterile (i.e., no uterus or no ovaries; females who have tubal ligation [tubes tied or cut] are not considered surgically sterile), or (3) willing to use 2 acceptable forms of birth control (i.e., barrier and spermicide, intrauterine device and barrier or spermicide, or birth control pill and barrier or spermicide). Male subjects with partners of child-bearing potential must use barrier contraception in addition to a second method of contraception used by their female partners. Male subjects should be advised to abstain from sexual intercourse with pregnant women or use condoms. Male and female subjects must be willing and able to continue contraception for 2 months after their last dose of study treatment. Female subjects of childbearing potential must have a negative pregnancy test result at both the Screening Visit and the Day 1 Visit. |
|
| E.4 | Principal exclusion criteria |
Unless otherwise specified, candidates will be excluded from study entry if any of the following exclusion criteria exist at the time of the Day 1 Visit:
1. Has a Mini Mental State Examination score <26.
2. History or clinical features consistent with an atypical parkinsonian syndrome.
3. Any significant non-PD central nervous system disorder.
4. Any significant AXIS I psychiatric disease as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition-Revised.
5. History of surgical intervention for PD.
6. History of malignancy unless an exemption has been granted.
7. History of severe allergic or anaphylactic reactions to any drug.
8. History of human immunodeficiency virus.
9. Hb A1c >7.0% at the Screening Visit.
10. Abnormal laboratory results from the Screening Visit in a quantitative test of G6PD activity or evidence of G6PD deficiency in any qualitative test (unless subsequent quantitative testing confirms activity within the normal range). Subjects with a family history of G6PD deficiency, subjects with immediate family members diagnosed with sickle cell anaemia or deaths due to neonaal jaundice, or subjects with a past history of hemolytic anemia or severe hemolysis are also to be excluded from the study.
11. Clinically significant hypertension, cardiac, gastrointestinal, renal, pulmonary, hematopoietic, endochrine, hepatic, immunologic, metabolic, urologic, dermatologic, and/or other major disease, unless an exemption has been granted.
12. Serious infection within 1 month prior to Day 1.
13. Positive for hepatitis C antibody or hepatitis B surface antigen.
14. Abnormal laboratory results from the Screening Visit as follows: aspartate aminotransferase, alanine aminotransferase, total bilirubin, gammaglutamyl-transferase levels >1.5 x ULN; serum lipase >ULN; white blood cell count <4,000 cells/mm3; hemoglobin <10 g/dL, or any other abnormal laboratory value that could interfere with the assessment of safety.
15. Clinically significant baseline ECG or laboratory abnormalities, unless exempted.
16. Orthostatic hypotension as defined by a decrease in systolic BP of >20 mmHg or in diastolic BP of >10 mmHg measured 2 minutes after changing from a supine to standing position.
17. For subjects receiving treatment with non-centrally acting anti-hypertensive agents, any change in dosing regimen within the 3 months prior to Day 1.
18. Participation in any other investigational drug study within the 4 weeks prior to Day 1 or within 5 half-lives of the investigational treatment, whichever is longer.
19. Treatment with any disallowed PD medication, centrally acting dopaminergic antagonists, or any change in L-DOPA or dopaminergic therapy dosing within the 4 weeks prior to Day 1.
20. For subjects receiving concomitant treatment with allowed dopaminergic therapies:
. Within the 4 weeks prior to Day 1: Any change in dosing (dose and/or frequency) of any 2D6 substrate (antidepressants or opioid narcotics)
· Within the 2 weeks prior to Day 1: Treatment with any known CYP inhibitors
21. Use of estrogen-containing depot or intrauterine contraceptives or second-generation estrogen-containing oral contraceptives within the 4 weeks prior to Day 1 or at any time during the study.
22. Any change in dosing regimen within the 4 weeks prior to Day 1 for any of the following:
. any central nervous system active therapy
· maintenance or prophylactic therapy for stable medical conditions,
· contraceptives,
· approved over-the-counter medications, and/or
· alternative health preparations and procedures.
23. Female subjects who are pregnant or are planning to become pregnant within the next 6 months following study entry, or who are currently breastfeeding.
24. History of drug or alcohol abuse as defined by the DSM IV-TR within 1 year prior to randomization into this trial.
25. Donation of blood or plasma in excess of 500 mL within 3 months of Day 1.
26. Caffeine intake within the 24 hours prior to Day 1.
27. Unwillingness or inability to comply with the requirements of the protocol including the presence of any condition that is likely to affect the subject’s ability to comply with the protocol.
28. Any other reasons that, in the opinion of the Investigator and/or the Sponsor, the subject is determined to be unsuitable for enrollment in this study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoints are:
· The number and proportion of subjects with AEs.
· Assessment of clinical laboratory parameters.
· Assessment of vital signs.
· Assessment of ECG parameters.
|
|
| 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 | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| 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 | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 | Yes |
| 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 | 5 |
| 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 | 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
|
DATABASE LOCK:
This is the End of Study definition being used routinely by Biogen Idec.
|
|
| 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 | 0 |
| 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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