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 |
The primary objective of this study is to evaluate the degree and frequency of response to Phenoptin treatment, as demonstrated by a reduction in blood phenylalanine (Phe) level, among subjects with phenylketonuria (PKU) who have elevated blood Phe levels. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are as follows:
To evaluate the safety of Phenoptin treatment in this subject population·
To identify individuals in this subject population who respond to Phenoptin treatment with a reduction in blood Phe level |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Age = or > 8 years· 2. Blood Phe level = or > 600 μmol/L at screening· Clinical diagnosis of PKU with hyperphenylalaninemia documented by past medical history of at least one blood Phe measurement = or > 360 μmol/L (6 mg/dL) · 3. 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, after the nature of the study has been explained· 4. Negative urine pregnancy test at screening (non-sterile females of child-bearing potential only)· Currently using acceptable birth control measures, as determined by the investigator, and willing to continue to use acceptable birth control measures while participating in the study (if sexually active and non-sterile)· 5. Willing and able to comply with study procedures· 6. Willing to continue current diet unchanged while participating in the study |
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E.4 | Principal exclusion criteria |
1. Use of any investigational agent within 30 days prior to screening, or requirement for any investigational agent or vaccine prior to completion of all scheduled study assessments· 2. Pregnant or breastfeeding, or considering pregnancy· 3. ALT > 5 times the upper limit of normal (i.e., Grade 3 or higher based on WHO Toxicity Criteria) at screening· 4. 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, or organ transplantation)· Serious neuropsychiatric illness (e.g., major depression) not currently under medical control· 5. Requirement for concomitant treatment with any drug known to inhibit folate synthesis (e.g., methotrexate)· Concurrent use of levodopa· 6. Clinical diagnosis of primary BH4 deficiency |
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E.5 End points |
E.5.1 | Primary end point(s) |
The percentage of subjects who experience a response to Phenoptin on Day 8 will be calculated, with response defined as a reduction in blood Phe level of = or > 30% compared with baseline in subjects with a baseline Phe of < 1200 mmol/L or a reduction of = or > 50% in subjects with a baseline Phe of = or >1200 mmol/L. In addition, the mean change in blood Phe levels at Day 8 will be estimated in the two baseline strata (<1200 mmol/L and = or > 1200 mmol/L). |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
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.8.5 | 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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End of the trial is the last visit of the last patient 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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 6 |