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

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ClinicalTrials.gov Identifier: NCT03001011
Recruitment Status : Completed
First Posted : December 22, 2016
Results First Posted : July 28, 2020
Last Update Posted : March 25, 2022
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Hyperphosphatemia Drug: Placebo Drug: Sevelamer Carbonate (GZ419831) Phase 3

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 202 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 7, 2017
Actual Primary Completion Date : August 16, 2019
Actual Study Completion Date : August 16, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases

Arm Intervention/treatment
Placebo Comparator: Placebo
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

Pharmaceutical form: tablet

Route of administration: oral


Experimental: Renvela
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)

Pharmaceutical form: tablet

Route of administration: oral

Other Name: Renvela




Primary Outcome Measures :
  1. Change From Baseline in Serum Phosphorus at Week 8 [ Time Frame: Baseline, 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.


Secondary Outcome Measures :
  1. Change From Baseline in Total Cholesterol at Week 8 [ Time Frame: Baseline, Week 8 ]
    Missing Week 8 data were imputed by LOCF method.

  2. Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 8 [ Time Frame: Baseline, Week 8 ]
    Missing Week 8 data were imputed by LOCF method.

  3. Change From Baseline in Calcium-Phosphorus Product at Week 8 [ Time Frame: Baseline, Week 8 ]
    Missing Week 8 data were imputed by LOCF method.

  4. Change From Baseline in Intact Parathyroid Hormone (Ipth) Level at Week 8 [ Time Frame: Baseline, Week 8 ]
    Missing Week 8 data were imputed by LOCF method.

  5. Percentage of Participants Reaching the Target Serum Phosphorus Level (4.6 mg/dL [1.49 mmol/L]) at Week 8 [ Time Frame: Week 8 ]
    Missing Week 8 data were imputed by LOCF method.

  6. Change From Baseline in Serum Phosphorus Level at Week 4 [ Time Frame: Baseline, Week 4 ]
    Missing Week 4 data were imputed by LOCF method.

  7. Number of Participants With Treatment Emergent Adverse Event [ Time Frame: From first dose of IMP to the last dose of IMP +3 days i.e. up to Day 59 ]
    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.

  8. Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters [ Time Frame: From first dose of IMP to the last dose of IMP +3 days i.e. up to Day 59 ]

    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)

  9. Number of Participants With Clinically Significant Laboratory Abnormalities: Metabolic Parameters [ Time Frame: From first dose of IMP to the last dose of IMP +3 days i.e. up to Day 59 ]

    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.

  10. Number of Participants With Clinically Significant Laboratory Abnormalities: Electrolytes [ Time Frame: From first dose of IMP to the last dose of IMP +3 days i.e. up to Day 59 ]

    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.


  11. Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters [ Time Frame: From first dose of IMP to the last dose of IMP +3 days i.e. up to Day 59 ]

    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.


  12. Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Parameters [ Time Frame: From first dose of IMP to the last dose of IMP +3 days i.e. up to Day 59 ]

    Criteria for potentially clinically significant abnormalities:

    Alanine Aminotransferase (ALT): >3 ULN; >5 ULN; >10 ULN; Aspartate aminotransferase (AST): >3 ULN.


  13. Number of Participants With Clinically Significant Vital Signs Abnormalities [ Time Frame: From first dose of IMP to the last dose of IMP +3 days i.e. up to Day 59 ]

    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.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03001011


Locations
Show Show 38 study locations
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
  Study Documents (Full-Text)

Documents provided by Sanofi:
Study Protocol  [PDF] April 13, 2018
Statistical Analysis Plan  [PDF] September 17, 2019

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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03001011    
Other Study ID Numbers: EFC14011
U1111-1161-9850 ( Other Identifier: UTN )
First Posted: December 22, 2016    Key Record Dates
Results First Posted: July 28, 2020
Last Update Posted: March 25, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Hyperphosphatemia
Urologic Diseases
Renal Insufficiency
Phosphorus Metabolism Disorders
Metabolic Diseases
Sevelamer
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action