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

• Sponsor: Sanofi (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03001011
• Collaborator: (none)
• Enrollment: 202
• Locations: 38
• Arms: 2
• Actual Duration (Months): 26.3
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Study Design

• Study Type: Interventional
• 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: Jun 7, 2017
• Actual Primary Completion Date: Aug 16, 2019
• Actual Study Completion Date: Aug 16, 2019

Arms and Interventions

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 Names: Renvela

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Serum Phosphorus at Week 8 [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 [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 [Baseline, Week 8]

   Missing Week 8 data were imputed by LOCF method.

3. Change From Baseline in Calcium-Phosphorus Product at Week 8 [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 [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 [Week 8]

   Missing Week 8 data were imputed by LOCF method.

6. Change From Baseline in Serum Phosphorus Level at Week 4 [Baseline, Week 4]

   Missing Week 4 data were imputed by LOCF method.

7. Number of Participants With Treatment Emergent Adverse Event [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 [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 [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 [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 [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 [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 [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 1560003	Beijing		China	100034
2	Investigational Site Number 1560026	Cangzhou		China	061000
3	Investigational Site Number 1560015	Changchun		China	130021
4	Investigational Site Number 1560011	Changsha		China	410011
5	Investigational Site Number 1560030	Chongqing		China	400038
6	Investigational Site Number 1560019	Dalian		China	116011
7	Investigational Site Number 1560013	Fuzhou		China	350005
8	Investigational Site Number 1560001	Guangzhou		China	510080
9	Investigational Site Number 1560027	Guangzhou		China	510120
10	Investigational Site Number 1560037	Guilin		China
11	Investigational Site Number 1560031	Haikou		China	570311
12	Investigational Site Number 1560036	Hengyang		China	421001
13	Investigational Site Number 1560039	Hengyang		China	421001
14	Investigational Site Number 1560023	Hohhot		China	010050
15	Investigational Site Number 1560033	Kunming		China
16	Investigational Site Number 1560034	Kunming		China
17	Investigational Site Number 1560006	Lanzhou		China	730030
18	Investigational Site Number 1560004	Nanchang		China	330006
19	Investigational Site Number 1560005	Nanchang		China	330006
20	Investigational Site Number 1560032	Nanchang		China	330006
21	Investigational Site Number 1560017	Nanjing		China	210011
22	Investigational Site Number 1560029	Nanning		China
23	Investigational Site Number 1560028	Ningbo		China
24	Investigational Site Number 1560002	Shanghai		China	200025
25	Investigational Site Number 1560007	Shanghai		China	200072
26	Investigational Site Number 1560021	Shenyang		China	110004
27	Investigational Site Number 1560038	Shenyang		China	110016
28	Investigational Site Number 1560025	Shijiazhuang		China	050000
29	Investigational Site Number 1560022	Taiyuan		China	030001
30	Investigational Site Number 1560012	Tianjin		China	300052
31	Investigational Site Number 1560014	Tianjin		China	300121
32	Investigational Site Number 1560010	Wuhan		China	430030
33	Investigational Site Number 1560008	Xi'An		China	710061
34	Investigational Site Number 1560020	Xiamen		China	361003
35	Investigational Site Number 1560018	Xiamen		China	361004
36	Investigational Site Number 1560035	Xuzhou		China	221002
37	Investigational Site Number 1560024	Yinchuan		China	750004
38	Investigational Site Number 1560016	Zhanjiang		China	524001

Sponsors and Collaborators

• Sanofi

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

• Study Protocol - Apr 13, 2018
• Statistical Analysis Plan - Sep 17, 2019

More Information

Publications

None provided.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT03001011
• Other Study ID Numbers: EFC14011; U1111-1161-9850
• First Posted: Dec 22, 2016
• Last Update Posted: Mar 25, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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: Kidney Diseases; Renal Insufficiency, Chronic; Hyperphosphatemia; Sevelamer

Study Results

Participant Flow

Recruitment Details	Study was conducted at 38 centers in China. A total of 482 participants were screened between 07 June 2017 & 30 May 2019, of which 280 participants were screen failures. Screen failures were mainly due to serum phosphorus level greater than or equal to >=5.5 milligrams per deciliter (mg/dL) (1.78 millimoles per litre [mmol/L]) at screening visit.
Pre-assignment Detail	A total of 202 participants were randomized in the study. Randomization was stratified according to screening serum phosphorus level (>=5.5 - 6.0 mg/dL [1.78 - 1.94 mmol/L] and >6.0 mg/dL [1.94 mmol/L]). Assignment to arms was done centrally using interactive voice/web response system in 1:1 ratio (Renvela [sevelamer carbonate]: placebo).

Arm/Group Title	Placebo	Renvela
Arm/Group Description	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).	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).
Period Title: Overall Study
STARTED	101	101
COMPLETED	74	80
NOT COMPLETED	27	21

Baseline Characteristics

Arm/Group Title	Placebo	Renvela	Total
Arm/Group Description	Participants received placebo (for 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).	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).	Total of all reporting groups
Overall Participants	101	101	202
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.9 (12.4)	50.6 (13.5)	50.7 (12.9)
Sex: Female, Male (Count of Participants)
Female	46 45.5%	48 47.5%	94 46.5%
Male	55 54.5%	53 52.5%	108 53.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	101 100%	101 100%	202 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Serum Phosphorus at Week 8
Description	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.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Modified intention to treat (mITT) population: all participants who were randomized, received at least 1 dose of IMP & had both baseline assessment & at least 1 post-baseline assessment of phosphorus measure. Here, number analyzed = participants with available data at specified time points.

Arm/Group Title	Placebo	Renvela
Arm/Group Description	Participants received placebo (for 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).	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).
Measure Participants	93	98
Baseline	2.090	2.095
Change at Week 8	0.010	-0.200

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Renvela
	Comments	A hierarchical testing procedure was used to control type I error & handle multiple secondary endpoint analyses. Testing was then performed sequentially in order outcome measures (OM) are reported. The hierarchical testing sequence continued only when previous OM was statistically significant at 0.05 level.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for statistical significance at 0.05.
	Method	Wilcoxon rank sum test
	Comments
Method of Estimation	Estimation Parameter	Median difference (Renvela - Placebo)
	Estimated Value	-0.210
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Renvela Vs. Placebo

2. Secondary Outcome

Title	Change From Baseline in Total Cholesterol at Week 8
Description	Missing Week 8 data were imputed by LOCF method.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Placebo	Renvela
Arm/Group Description	Participants received placebo (for 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).	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).
Measure Participants	82	89
Median (Full Range) [mmol/L]	-0.115	-0.830

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Placebo	Renvela
Arm/Group Description	Participants received placebo (for 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).	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).
Measure Participants	81	86
Median (Full Range) [mmol/L]	-0.030	-0.830

4. Secondary Outcome

Title	Change From Baseline in Calcium-Phosphorus Product at Week 8
Description	Missing Week 8 data were imputed by LOCF method.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Placebo	Renvela
Arm/Group Description	Participants received placebo (for 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).	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).
Measure Participants	90	97
Median (Full Range) [mmol^2/L^2]	0.0200	-0.4960

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Placebo	Renvela
Arm/Group Description	Participants received placebo (for 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).	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).
Measure Participants	91	97
Median (Full Range) [nanogram per liter (ng/L)]	7.2380	0.0000

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Placebo	Renvela
Arm/Group Description	Participants received placebo (for 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).	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).
Measure Participants	91	97
Number [percentage of participants]	6.6 6.5%	15.5 15.3%

7. Secondary Outcome

Title	Change From Baseline in Serum Phosphorus Level at Week 4
Description	Missing Week 4 data were imputed by LOCF method.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Placebo	Renvela
Arm/Group Description	Participants received placebo (for 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).	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).
Measure Participants	91	97
Median (Full Range) [mmol/L]	-0.020	-0.240

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population that consisted of all randomized participants who received at least one dose of IMP.

Arm/Group Title	Placebo	Renvela
Arm/Group Description	Participants received placebo (for 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).	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).
Measure Participants	101	101
Any TEAE	86 85.1%	83 82.2%
Any Treatment emergent SAE	31 30.7%	26 25.7%
any TEAE leading to permanent discontinuation	21 20.8%	12 11.9%

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population. Here, number analyzed = participants with available data for the specified categories.

Arm/Group Title	Placebo	Renvela
Arm/Group Description	Participants received placebo (for 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]).	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).
Measure Participants	101	101
Hemoglobin <=115 g/L (M) or <=95 g/L (F)	59 58.4%	54 53.5%
Hemoglobin >=185 g/L (M) or >=165 g/L (F)	0 0%	0 0%
Hemoglobin DFB >=20 g/L	9 8.9%	6 5.9%
Hematocrit <=0.37 v/v (M) or <=0.32 v/v (F)	68 67.3%	67 66.3%
Hematocrit >0.55 v/v (M) or >=0.5 v/v (F)	0 0%	0 0%
RBC >=6 Tera/L	0 0%	1 1%
Platelets <100 Giga/L	3 3%	4 4%
Platelets >=700 Giga/L	0 0%	0 0%
WBC <3.0 Giga/L (NB) or <2.0 Giga/L (B)	2 2%	0 0%
WBC >=16.0 Giga/L	0 0%	0 0%
Neutrophils <1.5 Giga/L (NB) or <1.0 Giga/L (B)	0 0%	0 0%
Lymphocytes >4 Giga/L	0 0%	0 0%
Monocytes >0.7 Giga/L	0 0%	0 0%
Basophils >0.1 Giga/L	0 0%	0 0%
Eosinophils >0.5 Giga/L or >ULN (ULN >=0.5 Giga/L)	4 4%	6 5.9%

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population. Here, number analyzed = participants with available data for specified categories.

Arm/Group Title	Placebo	Renvela
Arm/Group Description	Participants received placebo (for 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).	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).
Measure Participants	101	101
Triglycerides: >=4.6 mmol/L	0 0%	2 2%
Glucose: =< 3.9 mmol/L and < LLN	1 1%	1 1%
Glucose: >=11.1 mmol/L(unfas); >=7 mmol/L(fas)	5 5%	6 5.9%
Albumin: <= 25 g/L	1 1%	0 0%

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population. Here, number analyzed = participants with available data for specified categories.

Arm/Group Title	Placebo	Renvela
Arm/Group Description	Participants received placebo (for 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).	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).
Measure Participants	101	101
Sodium <=129 mmol/L	1 1%	3 3%
Sodium >=160 mmol/L	0 0%	0 0%
Potassium <3 mmol/L	0 0%	0 0%
Potassium >=5.5 mmol/L	36 35.6%	46 45.5%
Chloride <80 mmol/L	0 0%	2 2%
Chloride >115 mmol/L	0 0%	0 0%

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population. Here, number analyzed = participants with available data for specified categories.

Arm/Group Title	Placebo	Renvela
Arm/Group Description	Participants received placebo (for 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).	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).
Measure Participants	101	101
Creatinine >=150 micromol/L	84 83.2%	89 88.1%
Creatinine >=30% change from baseline	15 14.9%	33 32.7%
Creatinine >=100% change from baseline	3 3%	3 3%
Creatinine Clearance <15 mL/min	77 76.2%	81 80.2%
Creatinine clearance >=15 to <30 mL/min	6 5.9%	8 7.9%
Creatinine clearance >=30 to <60 mL/min	1 1%	0 0%
Creatinine clearance >=60 to <90 mL/min	0 0%	0 0%
Blood Urea Nitrogen >=17 mmol/L	77 76.2%	83 82.2%
Uric acid <120 micromol/L	0 0%	0 0%
Uric acid >408 micromol/L	56 55.4%	67 66.3%
GFR < 15 mL/min/1.73m^2	82 81.2%	86 85.1%
GFR >= 15 - < 30 mL/min/1.73m^2	2 2%	3 3%
GFR >= 30 - < 60 mL/min/1.73m^2	0 0%	0 0%
GFR >= 60 - < 90 mL/min/1.73m^2	0 0%	0 0%

13. Secondary Outcome

Title	Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Parameters
Description	Criteria for potentially clinically significant abnormalities: Alanine Aminotransferase (ALT): >3 ULN; >5 ULN; >10 ULN; Aspartate aminotransferase (AST): >3 ULN.
Time Frame	From first dose of IMP to the last dose of IMP +3 days i.e. up to Day 59

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population. Here, number analyzed = participants with available data for specified categories.

Arm/Group Title	Placebo	Renvela
Arm/Group Description	Participants received placebo (for 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).	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).
Measure Participants	101	101
ALT >3 ULN	1 1%	0 0%
ALT >5 ULN	1 1%	0 0%
ALT >10 ULN	0 0%	0 0%
AST >3 ULN	0 0%	0 0%

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population. Here, number analyzed = participants with available data for specified categories.

Arm/Group Title	Placebo	Renvela
Arm/Group Description	Participants received placebo (for 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).	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).
Measure Participants	101	101
SBP (supine) <=95 mmHg and DFB >=20 mmHg	0 0%	0 0%
SBP (supine) >=160 mmHg and IFB >=20 mmHg	17 16.8%	12 11.9%
DBP (supine) <=45 mmHg and DFB >=10 mmHg	0 0%	0 0%
DBP (supine) >=110 mmHg and IFB >=10 mmHg	2 2%	3 3%
HR (supine) <=50 bpm and DFB >= 20 bpm	0 0%	0 0%
HR (supine) >=120 bpm and IFB >=20 bpm	0 0%	0 0%
Weight >=5% DFB	12 11.9%	7 6.9%
Weight >=5% IFB	14 13.9%	9 8.9%

Adverse Events

Time Frame	Reported AEs are TEAEs that is AEs that developed/worsened or became serious during the TEAE period (time from the first dose of IMP to the last dose of IMP+3 days i.e. Day 59).
Adverse Event Reporting Description	Analysis was performed on safety population.
Arm/Group Title	Placebo		Renvela
Arm/Group Description	Participants received placebo (for Renvela) orally TID with meals up to 8 weeks as directed by physician and were titrated to reach a target goal of serum phosphorus <=4.6 mg/dL (<=1.49 mmol/L).		Participants received Renvela orally TID with meals up to 8 weeks as directed by physician and were titrated to reach a target goal of serum phosphorus <=4.6 mg/dL (<=1.49 mmol/L).
All Cause Mortality
	Placebo		Renvela
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/101 (0%)		0/101 (0%)
Serious Adverse Events
	Placebo		Renvela
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/101 (30.7%)		26/101 (25.7%)
Blood and lymphatic system disorders
Anaemia	1/101 (1%)	1	0/101 (0%)	0
Cardiac disorders
Angina Pectoris	1/101 (1%)	1	0/101 (0%)	0
Cardiac Failure	1/101 (1%)	1	1/101 (1%)	1
Cardiac Failure Acute	1/101 (1%)	1	0/101 (0%)	0
Eye disorders
Cataract	0/101 (0%)	0	1/101 (1%)	1
Gastrointestinal disorders
Gastrointestinal Haemorrhage	1/101 (1%)	1	0/101 (0%)	0
Inguinal Hernia	0/101 (0%)	0	1/101 (1%)	1
Hepatobiliary disorders
Cholecystitis Acute	0/101 (0%)	0	1/101 (1%)	1
Cholelithiasis	0/101 (0%)	0	1/101 (1%)	1
Infections and infestations
Lung Infection	2/101 (2%)	2	2/101 (2%)	2
Pulmonary Tuberculosis	0/101 (0%)	0	1/101 (1%)	1
Urinary Tract Infection	1/101 (1%)	1	0/101 (0%)	0
Injury, poisoning and procedural complications
Femur Fracture	0/101 (0%)	0	1/101 (1%)	1
Metabolism and nutrition disorders
Hyperkalaemia	2/101 (2%)	2	2/101 (2%)	2
Musculoskeletal and connective tissue disorders
Costochondritis	0/101 (0%)	0	1/101 (1%)	1
Intervertebral Disc Disorder	1/101 (1%)	1	0/101 (0%)	0
Intervertebral Disc Protrusion	1/101 (1%)	1	0/101 (0%)	0
Myofascitis	1/101 (1%)	1	0/101 (0%)	0
Nervous system disorders
Cerebral Haemorrhage	1/101 (1%)	1	0/101 (0%)	0
Renal and urinary disorders
Acute Kidney Injury	1/101 (1%)	1	0/101 (0%)	0
Azotaemia	4/101 (4%)	4	1/101 (1%)	1
Chronic Kidney Disease	13/101 (12.9%)	14	8/101 (7.9%)	8
Diabetic Nephropathy	0/101 (0%)	0	1/101 (1%)	1
End Stage Renal Disease	7/101 (6.9%)	8	9/101 (8.9%)	9
Glomerulonephritis Chronic	0/101 (0%)	0	1/101 (1%)	1
Renal Impairment	0/101 (0%)	0	1/101 (1%)	1
Skin and subcutaneous tissue disorders
Psoriasis	1/101 (1%)	1	0/101 (0%)	0
Surgical and medical procedures
Arteriovenous Fistula Operation	1/101 (1%)	1	0/101 (0%)	0
Vascular disorders
Hypertension	0/101 (0%)	0	1/101 (1%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Renvela
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	52/101 (51.5%)		60/101 (59.4%)
Gastrointestinal disorders
Abdominal Distension	5/101 (5%)	5	6/101 (5.9%)	7
Constipation	5/101 (5%)	5	7/101 (6.9%)	8
Diarrhoea	8/101 (7.9%)	10	5/101 (5%)	5
Nausea	15/101 (14.9%)	15	10/101 (9.9%)	11
Vomiting	13/101 (12.9%)	17	12/101 (11.9%)	20
General disorders
Oedema Peripheral	9/101 (8.9%)	10	14/101 (13.9%)	14
Infections and infestations
Upper Respiratory Tract Infection	9/101 (8.9%)	9	8/101 (7.9%)	8
Metabolism and nutrition disorders
Decreased Appetite	11/101 (10.9%)	13	4/101 (4%)	4
Hyperkalaemia	18/101 (17.8%)	24	25/101 (24.8%)	31
Hypocalcaemia	8/101 (7.9%)	8	3/101 (3%)	3
Metabolic Acidosis	7/101 (6.9%)	7	4/101 (4%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.