Evaluation of Renvela in Patients With Chronic Kidney Disease Not On Dialysis And Hyperphosphatemia In China

Study Overview
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Brief Summary
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Primary Objective: To demonstrate efficacy of Renvela tablets in the reduction of serum phosphorus in hyperphosphatemia in participants with chronic kidney disease not on dialysis. Secondary Objectives: To document the efficacy of Renvela tablets in the reduction of serum lipids (total cholesterol and low-density lipoprotein cholesterol [LDL-C]). To document the efficacy of Renvela tablets in the reduction of calcium-phosphorus product. To document the efficacy of Renvela tablets in the reduction of intact parathyroid hormone (iPTH). To document the efficacy of Renvela tablets in proportion of participants reaching the target serum phosphorus level 4.6 milligrams per decilitre (mg/dL) (1.47 millimoles per litre [mmol/L], inclusive). To evaluate safety of Renvela tablets.

Detailed Description
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The total duration of study period per participant was up to 14 weeks.

Official Title
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A Randomized, Double Blind, Parallel Group Study For Assessing The Efficacy And Safety Of Renvela® Tablets For The Treatment Of Hyperphosphatemia In Patients With Chronic Kidney Disease Not On Dialysis Versus Placebo

Conditions
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Hyperphosphatemia

Intervention / Treatment
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* Drug: Placebo
* Drug: Sevelamer Carbonate (GZ419831)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Participants with chronic kidney disease who had not been on dialysis, and were not expected to begin dialysis, or renal transplantation in the next 4 months from the screening visit. Had serum phosphorus measurement greater than or equal to (>=) 5.5 mg/dL (1.78 mmol/L) at screening visit (if participants were not on phosphate binder[s] at Screening Visit) OR at the end of Washout Period (if participants were on phosphate binder[s] at screening visit). Had the following laboratory measurements at screening visit: 25-hydroxy vitamin D >=10 nanograms per milliliter (ng/mL). intact parathyroid hormone, intact parathyroid hormone (iPTH) <=800 picograms per millilitre (pg/mL). Signed written informed consent. Exclusion criteria: Men or women below 18 years of age. Any technical/administrative reason that made it impossible to randomize the participant in the study. Was not of the level of understanding and willingness to cooperate with all visits and procedures, as described in the study protocol. Not yet received chronic kidney disease diet education before screening visit. Not willing and not able to avoid changes to diet during the study. Not willing or able to maintain screening doses of lipid lowering medication, 1, 25 dihydroxy vitamin D, and/or cinacalcet for the duration of the study, except for safety reasons. Not willing or not able to avoid antacids and phosphate binders containing aluminium, magnesium, calcium, or lanthanum for the duration of the study unless prescribed as an evening calcium supplement. Had participated in any other investigational drug studies within 30 days, or 5 half lives, whichever is longer, prior to screening visit. Conditions/situations such as: Participant was the Investigator or any Subinvestigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol. Uncooperative or any condition that could make the participant potentially non-compliant to the study procedures (for example, participants could not be contacted by phones as required in phone call visits). Evidence of active malignancy. Not on stable medical condition (for example, but not limited to, active ethanol or drug abuse [tobacco use acceptable]; documented poorly controlled diabetes mellitus, poorly controlled hypertension, active vasculitis, human immunodeficiency virus [HIV] infection), or had any clinically significant medical conditions. Had known hypersensitivity to sevelamer or any constituents of Renvela tablets. Had bowel obstruction, active dysphagia or swallowing disorder, or a predisposition to or current bowel obstruction, ileus, or severe gastrointestinal motility disorders including severe constipation. Using or plan to use anti-arrhythmic or anti-seizure medications for arrhythmia or seizure disorders. Was pregnant or breast-feeding. If the participant was female, and of childbearing potential (pre-menopausal and not surgically sterile), was not willing to use an effective contraceptive method throughout the study. Had any condition, which in the opinion of the investigator would prohibit the participant's inclusion in the study. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received placebo (for Renvela) orally 3 times per day (TID) for up to 8 weeks. One to five tablets were taken with meals, as directed by physician and were titrated (up to a maximum of 15 tablets per day) to reach a target goal of serum phosphorus less than or equal to (<=) 4.6 mg/dL (<=1.49 mmol/L). | Drug: Placebo<br>* Pharmaceutical form: tablet Route of administration: oral<br>|
| Experimental: Renvela<br>Participants received Renvela orally TID for up to 8 weeks. One to five tablets were taken with meals, as directed by physician and were titrated (up to a maximum of 15 tablets per day) to reach a target goal of serum phosphorus <=4.6 mg/dL (<=1.49 mmol/L). | Drug: Sevelamer Carbonate (GZ419831)<br>* Pharmaceutical form: tablet Route of administration: oral<br>* Other names: Renvela;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Serum Phosphorus at Week 8 | Baseline of serum phosphorus value was the last serum phosphorus level obtained before the first double-blind investigational medicinal product (IMP) dosing. Missing Week 8 data were imputed by last observation carried forward [LOCF] method. | Baseline, Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Cholesterol at Week 8 | Missing Week 8 data were imputed by LOCF method. | Baseline, Week 8 | 
| Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 8 | Missing Week 8 data were imputed by LOCF method. | Baseline, Week 8 | 
| Change From Baseline in Calcium-Phosphorus Product at Week 8 | Missing Week 8 data were imputed by LOCF method. | Baseline, Week 8 | 
| Change From Baseline in Intact Parathyroid Hormone (Ipth) Level at Week 8 | Missing Week 8 data were imputed by LOCF method. | Baseline, Week 8 | 
| Percentage of Participants Reaching the Target Serum Phosphorus Level (4.6 mg/dL [1.49 mmol/L]) at Week 8 | Missing Week 8 data were imputed by LOCF method. | Week 8 | 
| Change From Baseline in Serum Phosphorus Level at Week 4 | Missing Week 4 data were imputed by LOCF method. | Baseline, Week 4 | 
| Number of Participants With Treatment Emergent Adverse Event | Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an Adverse Event (AE) without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during TEAE period. On-treatment period was defined as the (time from the first dose of IMP to the last dose of IMP+3 days). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. | From first dose of IMP to the last dose of IMP +3 days i.e. up to Day 59 | 
| Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Criteria for potentially clinically significant abnormalities: Hemoglobin: <=115 g/L (Male[M]) or <=95 g/L (Female [F]); >=185 g/L (M) or >=165 g/L (F); Decrease from baseline (DFB) >=20 g/L Hematocrit: <=0.37 v/v (M) or <=0.32 v/v (F); >=0.55 v/v (M) or >=0.5 v/v (F) Red blood cells (RBC): >=6 Tera/L Platelets: <100 Giga/L; >=700 Giga/L White blood cells (WBC): <3.0 Giga/L (Non-Black [NB]) or <2.0 Giga/L (Black [B]); >=16.0 Giga/L Neutrophils: <1.5 Giga/L (NB) or <1.0 Giga/L (B); <1.0 Giga/L Lymphocytes: >4.0 Giga/L Monocytes: >0.7 Giga/L Basophils: >0.1 Giga/L Eosinophils: >0.5 Giga/L or >upper limit of normal (ULN) (if ULN >=0.5 Giga/L) | From first dose of IMP to the last dose of IMP +3 days i.e. up to Day 59 | 
| Number of Participants With Clinically Significant Laboratory Abnormalities: Metabolic Parameters | Criteria for potentially clinically significant abnormalities: Glucose: <=3.9 mmol/L and < lower limits of normal (LLN); >=11.1 mmol/L (unfasted [unfas]) or >=7 mmol/L (fasted [fas]) Triglycerides: >=4.6 mmol/L Albumin: <= 25 g/L. | From first dose of IMP to the last dose of IMP +3 days i.e. up to Day 59 | 
| Number of Participants With Clinically Significant Laboratory Abnormalities: Electrolytes | Criteria for potentially clinically significant abnormalities: Sodium: <=129 millimoles (mmol)/L; >=160 mmol/L Potassium: <3 mmol/L; >=5.5 mmol/L Chloride: <80 mmol/L; >115 mmol/L. | From first dose of IMP to the last dose of IMP +3 days i.e. up to Day 59 | 
| Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | Criteria for potentially clinically significant abnormalities: Creatinine: >=150 micromol/L; >=30% change from baseline, >=100% change from baseline Creatinine clearance: <15 mL/min; >=15 to <30 mL/min; >=30 to <60 mL/min; >=60 to <90 mL/min Blood urea nitrogen: >=17 mmol/L Uric acid: <120 micromol/L; >408 micromol/L Glomular Filtration Rate (GFR): < 15 mL/min/1.73m^2, >= 15 - < 30 mL/min/1.73m^2, >= 30 - < 60 mL/min/1.73m^2, >= 60 - < 90 mL/min/1.73m^2. | From first dose of IMP to the last dose of IMP +3 days i.e. up to Day 59 | 
| Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Parameters | Criteria for potentially clinically significant abnormalities: Alanine Aminotransferase (ALT): >3 ULN; >5 ULN; >10 ULN; Aspartate aminotransferase (AST): >3 ULN. | From first dose of IMP to the last dose of IMP +3 days i.e. up to Day 59 | 
| Number of Participants With Clinically Significant Vital Signs Abnormalities | Criteria for potentially clinically significant vital sign abnormalities: Systolic blood pressure (SBP) supine: <=95 millimeters of mercury (mmHg) and DFB >=20 mmHg; >=160 mmHg and increase from baseline (IFB) >=20 mmHg Diastolic blood pressure (DBP) supine: <=45 mmHg and DFB >=10 mmHg; >=110 mmHg and IFB >=10 mmHg Heart rate (HR) supine: <=50 beats per minute (bpm) and DFB >=20 bpm; >=120 bpm and IFB >=20 bpm Weight: >=5% DFB; >=5% IFB. | From first dose of IMP to the last dose of IMP +3 days i.e. up to Day 59 |