E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients on hemodialysis three times a week suffering from Uremic Pruritus (UP), uncontrolled by current medication(s) and/or treatment(s), will be enrolled.
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MedDRA Classification |
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 compare the efficacy of three times a week i.v. treatment with TRK-820 5µg versus placebo in hemodialysis patients with UP following completion of a four-week parallel-group treatment period.
Previously conducted Phase III studies showed a trend towards statistically significant results on efficacy for i.v. 5µg TRK-820 three times a week over placebo in a parallel group study with four weeks treatment as well as in a cross-over study with treatment periods of two weeks each. |
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E.2.2 | Secondary objectives of the trial |
·To investigate the efficacy of i.v. TRK-820 5µg over an 8-week treatment period. ·To investigate the maintenance of efficacy of i.v. TRK-820 5µg following a re randomization of the TRK-820 patients to continued i.v. TRK-820 5µg or placebo from Week 8 to Week 12. ·To assess the safety of i.v. TRK-820 5µg. ·To determine the pharmacokinetic (PK) characteristics of i.v. TRK-820 5µg in approximately 30 patients with UP on regular hemodialysis.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male and female patients at least 18 years of age. 2.Patient has a clinical diagnosis of UP due to ESRD which is uncontrolled by current medication(s) and/or treatment(s). 3.Patient on regular hemodialysis (or hemofiltration or hemodiafiltration), i.e. three times a week with a minimum duration of 12 hours per week and a minimum Kt/V of 1.2 for at least two months prior to the start of the one week run-in period. 4.Female patients must be surgically sterile; or postmenopausal for at least two years; or if of childbearing potential must have a negative serum pregnancy test and must agree to maintain adequate birth control practice during the study (e.g. hormonal contraceptives, contraceptive coil). Male and female patients must practice effective birth control during the study. 5.Patient capable of understanding the purposes and risks of the trial and has given written informed consent. 6.Patient has not taken, and agrees not to take, any medication or therapy prohibited by the protocol for the complete study period.
In order to qualify for treatment, patient must meet all of the following criteria at the end of the one week run-in period: 7.Patient completed ratings of worst itching intensity (VAS) at least 8 times out of 14 VAS assessments during the one week run-in period. 8.Patient has at least 3 VAS ratings of ≥ 50 mm during the one week run-in period. 9.Patient has a mean value of > 25 mm on the worst itching VAS during the one week run-in period.
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E.4 | Principal exclusion criteria |
1.Patient has pruritus other than secondary to ESRD. 2.Patient has pruritus only during the dialysis sessions. 3.Patient has an abnormal hepatic function based on an overall assessment by the investigator regarding medical history, physical examination and laboratory tests of hepatic function (ALT > 3 ULN, AST > 3 ULN). 4.Patient has a diagnosis of a malignant tumor. 5.Patient has an acute medical condition within 30 days prior the start of the one week run in period (Note: Subjects with an acute medical illness between screening and randomization must be re-screened after approval from the medical monitor). 6.Patient has an advanced, severe or unstable disease of any type other than ESRD (e.g. advanced chronic heart failure NYHA class III or IV, unstable angina, uncontrolled hypertension, uncontrolled diabetes mellitus, severe asthma). 7.Female patients who are pregnant or breast-feeding mothers. 8.Patient has any form of substance abuse/addiction (including drug or alcohol abuse) or psychiatric disorder or condition, which, in the opinion of the investigator, would prevent them from complying with the procedures detailed in the protocol. 9.Patient has a known hypersensitivity to opioids or the ingredients of the study medication. 10.Patient is taking any prohibited concomitant medication (please refer to section 7.2). 11. Patient is participating in another clinical trial (investigational drug or device) or was participating within 21 days prior the start of the one week run-in period. 12. Patient has a history of emotional instability or psychiatric disorder that makes them unsuitable for inclusion in the study. 13. Patient has already participated in a clinical study with TRK-820. In order to qualify for treatment, patient must not meet the following criterion at the end of the one week run-in period: 14. Patient has started any new emollient or oil bath within one week prior to the start of the one week run-in period.
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E.5 End points |
E.5.1 | Primary end point(s) |
The change in worst itching recorded on the Visual Analogue Scale (VAS) from baseline, which is the one week run-in period, to the end of Week 4 |
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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 | Yes |
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) | Yes |
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 | 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.8.3 |
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 | 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
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |