E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
We shall study patients with renal failure on dialysis. We shall particularly focus on patients with evidence of erythopoeitin stimulating agent (ESA) resistance. |
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E.1.1.1 | Medical condition in easily understood language |
Patients with renal failure on dialysis who are not responding well to a treatment for anaemia (EPO) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10014647 |
E.1.2 | Term | End stage renal failure |
E.1.2 | System Organ Class | 100000004857 |
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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 |
To study the effects Pentoxifylline in ESA resistant ESRD patients on haemodialysis.
The primary study endpoints is the ESA requirement relative to the Hb level (is there a difference in a randomised placebo controlled cross-over study)? |
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E.2.2 | Secondary objectives of the trial |
Secondary endpoints include:
• Safety analysis
• Hb values and ESA doses after 6 months of treatment.
• Blood sampling will be performed at the start of each hemodialysis session every month. These samples may be subjected to additional analyses to further characterize the pro- and anti-inflammatory effects of pentoxifylline including CRP.
• DNA telomere length shortening
• Radiological imaging will be performed at Baseline and at 6 months. The effect IMP has on the following radiological parameters will be examined:
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Be able to read and understand the written consent form, complete study-related procedures, and communicate with the study staff;
• Willing to comply with study restrictions;
• Between 18 and 65 years of age (inclusive).
• Diagnosis of clinically stable ESRD, as determined by the investigator;
• Requiring regular dialysis therapy for at least 12 weeks prior to first administration of study agent;
• Receiving treatment with IV or SC erythropoietin receptor agonist at least weekly (ie exclude Micera or other ESAs given fortnightly or monthly) for a minimum of 8 weeks prior to administration of study agent, requiring doses to remedy EPO-resistance (requiring >12,000iu equivalent of EPO per week), with evidence of stable hemoglobin levels;
• Baseline hemoglobin values between 9.0 and 12.0 g/dL before entering the study;
• CRP levels of ≥5 mg/L
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E.4 | Principal exclusion criteria |
• Clinically relevant abnormal history of physical and mental health other than conditions related to chronic kidney disease of patient, as determined by medical history taking (as judged by the investigator);
• Clinically relevant abnormal laboratory results, ECG, vital signs, or physical findings other than conditions related to chronic kidney disease of patient (as judged by the investigator);
• Subject has uncontrolled hypertension;
• Subject is unable to refrain from the use of disallowed concomitant medication from one week prior to the first study drug administration until follow-up assessments (see section 3.3);
• Participation in an investigational drug trial in the 3 months prior to administration of the initial dose of study drug that might interfere with the primary or secondary endpoints;
• Subject has undergone major surgery within six months prior to screening;
• Any other condition that in the opinion of the investigator would complicate or compromise the study (e.g. known haemoglobinopathy), or the well being of the subject.
• Females of child-bearing potential who are not willing to use contraception for the duration of the study.
• Subject is known hypersensitivity to the active constituent, pentoxifylline other methyl xanthines or any of the excipients.
• Subjects with recent cerebral haemorrhage, extensive retinal haemorrhage, acute myocardial infarction and severe cardiac arrhythmias
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E.5 End points |
E.5.1 | Primary end point(s) |
Endpoints: The primary study endpoints is the ESA requirement relative to the Hb level. |
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E.5.2 | Secondary end point(s) |
Secondary endpoints include:
• Safety analysis
• Hb values and ESA doses after 6 months of treatment.
• Blood sampling will be performed at the start of each hemodialysis session every month. These samples may be subjected to additional analyses to further characterize the pro- and anti-inflammatory effects of pentoxifylline including CRP.
• DNA telomere length shortening
• Radiological imaging will be performed at Baseline and at 6 months. The effect IMP has on the following radiological parameters will be examined:
_
_
_
_
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At the end of the study (cross-over design) |
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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 | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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.8.5 | 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 | No |
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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After the last visit of the last subject in the study |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |