E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Anemia in patients with Kidney Disease (CKD) |
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MedDRA Classification |
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 |
E.2.1 Main objective:
To define optimal factor (e.g. μg MK-2578 per U epoetin) for conversion of epoetin alfa or epoetin beta administered three times weekly (TIW), two times weekly (BIW), or weekly (QW) IV, to MK-2578, administered intravenously monthly or weekly that will maintain Hb at the baseline value (i.e., Hb change from baseline approximately 0 where baseline is defined as the average Hb value during the epoetin alfa/epoetin beta run-in period).
To assess the safety and tolerability of MK-2578 (IV) in hemodialysis patients previously treated with epoetin alfa or epoetin beta.
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E.2.2 | Secondary objectives of the trial |
E.2.2 Secondary Objective:
1) To evaluate the effect of dosing schedule (QW versus QM), for a given conversion factor, on change from baseline Hb.
2) To evaluate the performance of conversion factors over 12 weeks, as measured by change from baseline Hb by week and percentages of patients remaining within a target Hb range, requiring dose changes. and receiving transfusions. 3) To investigate the population pharmacokinetics of MK-2578 (IV) in patients with CKDon hemodialysis.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patient is a male or female between 18 to 65 years of age and weighs between 40 and 90 kg (dry weight) at Screening Visit 1.
Note: Patient must meet the current age criteria for Cohort 1. When Cohort 1 is completely enrolled and the cohort data has been analyzed, and if there are no safety issues with respect to age, the Sponsor may allow for patients for up to age 70 to be enrolled; however, this liberalization of age criterion will be communicated to sites.
Patient is unlikely to conceive, as indicated by at least one “yes” answer to the following questions:
a) Patient is a male. b) Patient is a surgically sterilized female. c) Patient is a postmenopausal female ≥ 45 years of age with > 2 years since last menses. d) Patient is a non-sterilized, premenopausal female and agrees to abstain from heterosexual activity or to use an adequate method of contraception.
Patient is on hemodialysis for ≥ 3 months at the time of Screening Visit 1 and is adequately dialyzed as indicated by a Kt/V ≥ 1.2.
Patient has received epoetin alfa or epoetin beta IV maintenance treatment for ≥ 6 months at the time of Screening Visit 1. In the 8 weeks prior to randomization, patient is continuously prescribed epoetin alfa or epoetin beta IV maintenance treatment at a dose between 50 to 250 U/kg/week that is administered on a consistent dosing schedule/ frequency. In the 3 weeks prior to randomization, a stable epoetin alfa or epoetin beta dose is required.
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E.4 | Principal exclusion criteria |
Patient has a life expectancy of less than 6 months.
Patient is scheduled to have a kidney transplant within the next 6 months. A patient on the waiting list for a cadaveric transplant may participate.
Patient has had a blood transfusion within 12 weeks of Screening Visit 1
Patient has had major surgery within the past 12 weeks or plans to have major surgery during the course of the study.
Patient has poorly controlled hypertension (as per Investigator opinion), or patient has had an episode of hypertension necessitating interruption of epoetin treatment in the 6 months before Screening Visit 1.
Patient has been diagnosed with human immunodeficiency virus.
Patient has severe congestive heart failure (New York Heart Association Class III or IV) with symptoms that occur at rest or with minimal activity.
Patient has a history of malignant neoplastic disease, except for adequately treated non-melanomatous skin lesions or carcinoma in situ of the cervix.
Patient has had a thrombotic vascular event, including but not limited to myocardial infarction (MI), cerebrovascular accident (stroke, CVA), transient ischemic attack (TIA), pulmonary embolus, or deep vein thrombosis (DVT) within 6 months of randomization.
Patient has a history of grand mal seizures within 6 months of randomization.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary: Change from baseline Hb at Week 4.
Secondary: Change from baseline Hb at Week 12.
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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 | 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) | 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 | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Multiple rising dose, first dose(s) administed in double-blind, placebo controlled crossover fashion |
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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 | Yes |
E.8.2.3.1 | Comparator description |
Initial dose(s) administered double-blind, placebo controlled; no placebo after crossover |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
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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See protocol; 28 day post-study follow up visit for all patients. |
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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 | 2 |
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 | 2 |