E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Classification code | 10034872 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and tolerability of long-term Phenoptin treatment in subjects with PKU. |
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E.2.2 | Secondary objectives of the trial |
To compare the safety and tolerability of three different doses of Phenoptin treatment in subjects with PKU. To determine the effect of various doses of Phenoptin on blood phenylalanine (Phe) levels. To evaluate the population pharmacokinetics of Phenoptin. To evaluate the ability of Phenoptin to reduce phenylalanine (Phe) levels over a 24-hour period. To evaluate the persistence of benefit of Phenoptin treatment in the subject population as evidenced by long-term control of blood Phe levels. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Eight years of age and older; Received ≥80% of the scheduled doses in Study PKU-003, unless removed from the study after exceeding the Phe alert level value; Willing and able to provide written informed consent or, in the case of subjects under the age of 18, provide written assent (if required) and written informed consent by a parent or legal guardian; Negative urine pregnancy test within 24 hours prior to enrollment (females of child-bearing potential only); Currently using acceptable birth control measures, as determined by the investigator, and willing to continue to use those measures while participating in the study; Willing and able to comply with study procedures; Willing to continue current diet unchanged while participating in the study. |
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E.4 | Principal exclusion criteria |
Perceived to be unreliable or unavailable for study participation or, if under the age of 18, have parents or legal guardians who are perceived to be unreliable or unavailable; Withdrew from, or otherwise did not successfully complete, study PKU-003, except for subjects who were removed from the study because their blood Phe exceeded the alert level; Expected to require any investigational agent or vaccine prior to completion of all scheduled study assessments; Pregnant or breastfeeding, or planning pregnancy; Concurrent disease or condition that would interfere with study participation or safety (e.g., seizure disorder, oral steroid-dependent asthma or other condition requiring oral or parenteral corticosteroid administration, or insulin-dependent diabetes); Requirement for concomitant treatment with any drug known to inhibit folate synthesis (e.g., methotrexate); Concurrent use of levodopa. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary measure of efficacy will be the blood Phe levels at the end of each dosing period.
The efficacy analyses will include all subjects enrolled in this study. Each subject will have data from three two-week periods at each of three pre-established doses, followed by a 10 mg/kg/day dose for 4 weeks, followed by a subject-specific dose for 12 weeks. Analysis of variance for crossover designs will be used to estimate average within-person changes in Phe level for the three dose levels. |
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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 | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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) | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Open-label extension study |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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.8.5 | The trial involves multiple Member States | Yes |
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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 11 |