E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Evaluation of the safety and equivalence of serum phosphate control of a
sevelamer carbonate tablet formulation in comparison with
Renvela® in chronic kidney disease patients on hemodialysis |
|
E.1.1.1 | Medical condition in easily understood language |
adult patients with hyperphosphataemia and chronic kidney disease (CKD) receiving hemodialysis |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
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 | 10020712 |
E.1.2 | Term | Hyperphosphatemia |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
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 evaluate the safety and tolerability of Synthon sevelamer carbonate (SVL) compared to Renvela® (Genzyme) tablets in patients with CKD on hemodialysis based on the evaluation of the incidence of adverse events and serious adverse events as well as compliance. |
|
E.2.2 | Secondary objectives of the trial |
To prove the equivalence of an oral test preparation containing 800 mg SVL as compared to Renvela® on the control of serum phosphorus in chronic kidney disease patients on hemodialysis |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
[1] Male and female Caucasian patients aged ≥18 years. Women of childbearing potential must have a
negative serum pregnancy test immediately prior to study entry, and meet the criteria for acceptable birth control (see paragraph 8.2), or female patients must be either post-menopausal for ≥1 year or surgically sterilised
[2] Stable maintenance hemodialysis regarding frequency (2 or 3 times per week) and dialysis parameters (e.g. average duration, type of dialyzer) for at least 3 months
[3] Life expectancy of at least 12 months
[4] At screening for patients not receiving previous treatment with phosphate binders or after 2 weeks
wash-out for patients who had previous therapy with phosphate binders: Serum phosphorus ≥1.78 mmol/l (≥5.5 mg/dl)
[5] Intact parathyroid hormone (iPTH) ≤87 pmol/l (≤800 pg/ml)
[6] Patients on stable diet and willing to follow stable diet
[7] Patients with ability to follow study instructions and likely to attend and complete all required visits
[8] Written informed consent of the patient. |
|
E.4 | Principal exclusion criteria |
[1] Hypersensitivity to sevelamer or to any of the excipients of the study drugs
[2] Poorly controlled diabetes mellitus (HbA1c >11%)
[3] Poorly controlled hypertension (blood pressure higher than 150/90 mm Hg)
[4] Iron overload: serum ferritin >800 ng/ml combined with TSAT >50%
[5] Swallowing disorder (dysphagia)
[6] Bowel obstruction
[7] Gastrointestinal motility disorders including:
- untreated or severe gastroparesis,
- diverticulosis,
- retention of gastric contents, or
- abnormal or irregular bowel motion.
[8] Active inflammatory bowel disease
[9] History of clinically relevant gastrointestinal surgery (excluding minor surgery, such as uncomplicated appendectomy, polypectomy or non-intestinal tract abdominal surgery, such as cholecystectomy)
[10] Severe vomiting
[11] Severe constipation
[12] Concomitant malignancy (except carcinoma in situ not needing other than local therapy and basal cell carcinoma of the skin)
[13] Use of:
- antacids,
- drugs that affect gastrointestinal motility,
- ciprofloxacin, (unless this medicinal product is administered at least one hour before or 3 hours after
sevelamer)
- phosphate binders containing aluminium, magnesium, calcium or lanthanum for the duration of
the study. A calcium supplement is acceptable if the dose remains unchanged between randomization
and completion of the study,
- levothyroxine,
- anti-arrhythmic medication,
- anti-seizure medication.
[14] Active vasculitis
[15] Alcohol /drug dependence or abuse (excluding tobacco abuse)
[16] Pregnancy or lactation
[17] Women of childbearing potential unable or unwilling to practice adequate contraceptive measures
[18] Positive serologic findings for human immunodeficiency virus (HIV) antibodies
[19] Simultaneous participation in another clinical study or participation in any clinical study involving an investigational drug within 1 month prior to start of the present study
[20] Severe physical or mental concomitant diseases that might hamper the realisation of the trial according to protocol
[21] Legal incapacity and/or other circumstances rendering the patient unable to understand the
nature, scope and possible consequences of the study
[22] Unreliability or lack of cooperation |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of treatment-emergent adverse events and percentage of
subjects who withdrew due to adverse events |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
After completion of study and closure of data base. |
|
E.5.2 | Secondary end point(s) |
Efficacy:
a) Time-weighted mean of the serum phosphorus concentration (determined from 4 measurements during the last 2 weeks of each 8-week double-blind treatment period) after treatment with
the test and the reference product
Safety:
a) Clinically relevant changes in vital signs from baseline to the end of treatment
b) Clinically relevant changes in safety laboratory parameters (hematology and biochemistry) from baseline to the end of treatment. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
After completion of study and closure of data base. |
|
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 | 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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 13 |
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
|
The clinical end of the trial is the last visit of the last patient undergoing the trial. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |