E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
In this study we will prospectively analyze the reduction of urinary oxalate excretion under the treatment with PLP in dosages of 5mg/kg/day up to 20 mg/kg/day and serum level response relationship with PLP as an i.v. solution used orally in 12 patients with primary hyperoxaluria type I as an inherited autosomal-recessive-disorder leading to increased endogenous oxalate production, urolithiasis and end stage renal disease.
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037671 |
E.1.2 | Term | Pyridoxine deficiency |
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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 endpoint of the study is the reduction of the urinary oxalate excretion (percentage change in urinary oxalate, expressed as mmol/1.73 m2 /day) at week 24 compared to baseline. The excess of endogenously produced oxalate is excreted via the urine in patients with primary hyperoxaluria. Because of the low solubility of oxalate as calcium salt, a high urinary oxalate excretion results in urolithiasis and/or progressive nephrolithiasis. Reduction of the urinary oxalate level is the standard measurement of treatment efficacy in patients with PH I.
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E.2.2 | Secondary objectives of the trial |
•The drug-response-relationship of pyridoxal-phosphate will be checked by repeated measurements of the serum pyridoxal-phosphate levels • Reduction of the plasma oxalate level as change in plasma oxalate concentration from baseline to week 6, 12, 18 and 24 •Reduction of the urinary oxalate excretion in patients with PH I at weeks 6, 12, 18 compared to baseline. •The safety of the oral application of an i.v. pyridoxal-phosphate solution will be determined.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•The drug-response-relationship of pyridoxal-phosphate will be checked by repeated measurements of the serum pyridoxal-phosphate levels • Reduction of the plasma oxalate level as change in plasma oxalate concentration from baseline to week 6, 12, 18 and 24 •Reduction of the urinary oxalate excretion in patients with PH I at weeks 6, 12, 18 compared to baseline. •The safety of the oral application of an i.v. pyridoxal-phosphate solution will be determined.
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E.4 | Principal exclusion criteria |
• Pregnant or lactating women • Women of child-bearing potential who are not using a highly effective contraception method with a pearl-index < 1. Highly effective contraception methods are oral, transdermal, injectable, or implanted contraceptives, IUD, abstinence, or sterile sexual partner and must agree to continue using such precautions during the pyridoxal-phosphate study. • Subjects post liver or kidney transplantation or combined transplantation • Chronic diarrhoea with the risk of malabsorption • Any other abnormal finding such as physical examination or laboratory evaluation, in the opinion of the investigator, is indicative of a disease that would compromise the safety taking pyridoxal-phosphate per os and the absorption. • Subjects participating in other clinical trials with investigational products 4 weeks prior to trial entry, during the trial and 4 weeks after the trial • Subjects who are unable to take the trial medication • Subjects who are unable to collect 24-hour urine samples or follow other study procedures • Subjects who are under treatment with L-Dopa, Isoniazid, D-Penicillamine (interactions between these drugs and pyridoxal-phosphate are known and might influence serum pyridoxal-phosphate levels) • Subjects with known allergies to substances of contents (e.g. Potassiumsorbet, raspberry sirupe) • Subjects confined to an institution on judicial or official behalf. • Subjects who are in dependency to the sponsor or the PI of the trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the reduction of the urinary oxalate excretion (percentage change in urinary oxalate, expressed as mmol/1.73 m2 /day) at week 24 compared to baseline. The excess of endogenously produced oxalate is excreted via the urine in patients with primary hyperoxaluria. Because of the low solubility of oxalate as calcium salt, a high urinary oxalate excretion results in urolithiasis and/or progressive nephrolithiasis. Reduction of the urinary oxalate level is the standard measurement of treatment efficacy in patients with PH I.
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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 | 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 | 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 | 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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
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 | Information not present in EudraCT |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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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Visit 5 after 24 weeks is end of treatment, end of trial is safety telephone interview week 28 |
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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 | 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 | 0 |
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 |