Hyperphosphatemia
Conditions
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.
Detailed description
The total duration of study period per participant was up to 14 weeks.
Interventions
DRUGPlacebo
Pharmaceutical form: tablet Route of administration: oral
DRUGSevelamer Carbonate (GZ419831)
Pharmaceutical form: tablet Route of administration: oral
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Change From Baseline in Calcium-Phosphorus Product at Week 8 | Baseline, Week 8 | Missing Week 8 data were imputed by LOCF method. |
| Change From Baseline in Intact Parathyroid Hormone (Ipth) Level at Week 8 | Baseline, Week 8 | Missing Week 8 data were imputed by LOCF method. |
| 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. |
| Change From Baseline in Serum Phosphorus Level at Week 4 | Baseline, Week 4 | Missing Week 4 data were imputed by LOCF method. |
| 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. |
| Change From Baseline in Total Cholesterol at Week 8 | Baseline, Week 8 | Missing Week 8 data were imputed by LOCF method. |
| 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. |
| 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) |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
China
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 details
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).
Participants by arm
| Arm | Count |
|---|---|
| Placebo 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). | 101 |
| 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). | 101 |
| Total | 202 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 3 |
| Overall Study | Chronic kidney disease lead to dialysis | 15 | 10 |
| Overall Study | Other than specified above | 3 | 8 |
Baseline characteristics
| Characteristic | Renvela | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 50.6 years STANDARD_DEVIATION 13.5 | 50.7 years STANDARD_DEVIATION 12.9 | 50.9 years STANDARD_DEVIATION 12.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 101 Participants | 202 Participants | 101 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 48 Participants | 94 Participants | 46 Participants |
| Sex: Female, Male Male | 53 Participants | 108 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 101 | 0 / 101 |
| other Total, other adverse events | 52 / 101 | 60 / 101 |
| serious Total, serious adverse events | 31 / 101 | 26 / 101 |
Outcome results
Primary
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.
Time frame: Baseline, Week 8
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Change From Baseline in Serum Phosphorus at Week 8 | Baseline | 2.090 mmol/L |
| Placebo | Change From Baseline in Serum Phosphorus at Week 8 | Change at Week 8 | 0.010 mmol/L |
| Renvela | Change From Baseline in Serum Phosphorus at Week 8 | Baseline | 2.095 mmol/L |
| Renvela | Change From Baseline in Serum Phosphorus at Week 8 | Change at Week 8 | -0.200 mmol/L |
Comparison: 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.p-value: <0.0001Wilcoxon rank sum test
Secondary
Change From Baseline in Calcium-Phosphorus Product at Week 8
Missing Week 8 data were imputed by LOCF method.
Time frame: Baseline, Week 8
Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change From Baseline in Calcium-Phosphorus Product at Week 8 | 0.0200 mmol^2/L^2 |
| Renvela | Change From Baseline in Calcium-Phosphorus Product at Week 8 | -0.4960 mmol^2/L^2 |
Secondary
Change From Baseline in Intact Parathyroid Hormone (Ipth) Level at Week 8
Missing Week 8 data were imputed by LOCF method.
Time frame: Baseline, Week 8
Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change From Baseline in Intact Parathyroid Hormone (Ipth) Level at Week 8 | 7.2380 nanogram per liter (ng/L) |
| Renvela | Change From Baseline in Intact Parathyroid Hormone (Ipth) Level at Week 8 | 0.0000 nanogram per liter (ng/L) |
Secondary
Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 8
Missing Week 8 data were imputed by LOCF method.
Time frame: Baseline, Week 8
Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 8 | -0.030 mmol/L |
| Renvela | Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 8 | -0.830 mmol/L |
Secondary
Change From Baseline in Serum Phosphorus Level at Week 4
Missing Week 4 data were imputed by LOCF method.
Time frame: Baseline, Week 4
Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change From Baseline in Serum Phosphorus Level at Week 4 | -0.020 mmol/L |
| Renvela | Change From Baseline in Serum Phosphorus Level at Week 4 | -0.240 mmol/L |
Secondary
Change From Baseline in Total Cholesterol at Week 8
Missing Week 8 data were imputed by LOCF method.
Time frame: Baseline, Week 8
Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change From Baseline in Total Cholesterol at Week 8 | -0.115 mmol/L |
| Renvela | Change From Baseline in Total Cholesterol at Week 8 | -0.830 mmol/L |
Secondary
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.
Time frame: From first dose of IMP to the last dose of IMP +3 days i.e. up to Day 59
Population: Analysis was performed on safety population. Here, number analyzed = participants with available data for specified categories.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Electrolytes | Sodium >=160 mmol/L | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Electrolytes | Potassium >=5.5 mmol/L | 36 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Electrolytes | Sodium <=129 mmol/L | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Electrolytes | Potassium <3 mmol/L | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Electrolytes | Chloride >115 mmol/L | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Electrolytes | Chloride <80 mmol/L | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Electrolytes | Chloride >115 mmol/L | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Electrolytes | Sodium <=129 mmol/L | 3 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Electrolytes | Sodium >=160 mmol/L | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Electrolytes | Potassium <3 mmol/L | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Electrolytes | Potassium >=5.5 mmol/L | 46 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Electrolytes | Chloride <80 mmol/L | 2 Participants |
Secondary
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)
Time frame: From first dose of IMP to the last dose of IMP +3 days i.e. up to Day 59
Population: Analysis was performed on safety population. Here, number analyzed = participants with available data for the specified categories.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Hematocrit >0.55 v/v (M) or >=0.5 v/v (F) | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | WBC <3.0 Giga/L (NB) or <2.0 Giga/L (B) | 2 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Hemoglobin >=185 g/L (M) or >=165 g/L (F) | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | WBC >=16.0 Giga/L | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | RBC >=6 Tera/L | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Neutrophils <1.5 Giga/L (NB) or <1.0 Giga/L (B) | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Hematocrit <=0.37 v/v (M) or <=0.32 v/v (F) | 68 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Lymphocytes >4 Giga/L | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Platelets <100 Giga/L | 3 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Monocytes >0.7 Giga/L | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Hemoglobin DFB >=20 g/L | 9 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Basophils >0.1 Giga/L | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Platelets >=700 Giga/L | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Eosinophils >0.5 Giga/L or >ULN (ULN >=0.5 Giga/L) | 4 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Hemoglobin <=115 g/L (M) or <=95 g/L (F) | 59 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Eosinophils >0.5 Giga/L or >ULN (ULN >=0.5 Giga/L) | 6 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Hemoglobin <=115 g/L (M) or <=95 g/L (F) | 54 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Hemoglobin >=185 g/L (M) or >=165 g/L (F) | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Hemoglobin DFB >=20 g/L | 6 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Hematocrit <=0.37 v/v (M) or <=0.32 v/v (F) | 67 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Hematocrit >0.55 v/v (M) or >=0.5 v/v (F) | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | RBC >=6 Tera/L | 1 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Platelets <100 Giga/L | 4 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Platelets >=700 Giga/L | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | WBC <3.0 Giga/L (NB) or <2.0 Giga/L (B) | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | WBC >=16.0 Giga/L | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Neutrophils <1.5 Giga/L (NB) or <1.0 Giga/L (B) | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Lymphocytes >4 Giga/L | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Monocytes >0.7 Giga/L | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters | Basophils >0.1 Giga/L | 0 Participants |
Secondary
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.
Time frame: From first dose of IMP to the last dose of IMP +3 days i.e. up to Day 59
Population: Analysis was performed on safety population. Here, number analyzed = participants with available data for specified categories.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Parameters | ALT >3 ULN | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Parameters | ALT >5 ULN | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Parameters | ALT >10 ULN | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Parameters | AST >3 ULN | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Parameters | AST >3 ULN | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Parameters | ALT >3 ULN | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Parameters | ALT >10 ULN | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Parameters | ALT >5 ULN | 0 Participants |
Secondary
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.
Time frame: From first dose of IMP to the last dose of IMP +3 days i.e. up to Day 59
Population: Analysis was performed on safety population. Here, number analyzed = participants with available data for specified categories.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Metabolic Parameters | Triglycerides: >=4.6 mmol/L | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Metabolic Parameters | Glucose: =< 3.9 mmol/L and < LLN | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Metabolic Parameters | Glucose: >=11.1 mmol/L(unfas); >=7 mmol/L(fas) | 5 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Metabolic Parameters | Albumin: <= 25 g/L | 1 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Metabolic Parameters | Albumin: <= 25 g/L | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Metabolic Parameters | Triglycerides: >=4.6 mmol/L | 2 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Metabolic Parameters | Glucose: >=11.1 mmol/L(unfas); >=7 mmol/L(fas) | 6 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Metabolic Parameters | Glucose: =< 3.9 mmol/L and < LLN | 1 Participants |
Secondary
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.
Time frame: From first dose of IMP to the last dose of IMP +3 days i.e. up to Day 59
Population: Analysis was performed on safety population. Here, number analyzed = participants with available data for specified categories.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | Creatinine >=150 micromol/L | 84 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | Creatinine >=30% change from baseline | 15 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | Creatinine >=100% change from baseline | 3 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | Creatinine Clearance <15 mL/min | 77 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | Creatinine clearance >=15 to <30 mL/min | 6 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | Creatinine clearance >=30 to <60 mL/min | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | Creatinine clearance >=60 to <90 mL/min | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | Blood Urea Nitrogen >=17 mmol/L | 77 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | Uric acid <120 micromol/L | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | Uric acid >408 micromol/L | 56 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | GFR < 15 mL/min/1.73m^2 | 82 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | GFR >= 15 - < 30 mL/min/1.73m^2 | 2 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | GFR >= 30 - < 60 mL/min/1.73m^2 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | GFR >= 60 - < 90 mL/min/1.73m^2 | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | GFR < 15 mL/min/1.73m^2 | 86 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | Creatinine >=150 micromol/L | 89 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | Blood Urea Nitrogen >=17 mmol/L | 83 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | Creatinine >=30% change from baseline | 33 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | GFR >= 30 - < 60 mL/min/1.73m^2 | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | Creatinine >=100% change from baseline | 3 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | Uric acid <120 micromol/L | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | Creatinine Clearance <15 mL/min | 81 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | GFR >= 15 - < 30 mL/min/1.73m^2 | 3 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | Creatinine clearance >=15 to <30 mL/min | 8 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | Uric acid >408 micromol/L | 67 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | Creatinine clearance >=30 to <60 mL/min | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | GFR >= 60 - < 90 mL/min/1.73m^2 | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Laboratory Abnormalities: Renal Function Parameters | Creatinine clearance >=60 to <90 mL/min | 0 Participants |
Secondary
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.
Time frame: From first dose of IMP to the last dose of IMP +3 days i.e. up to Day 59
Population: Analysis was performed on safety population. Here, number analyzed = participants with available data for specified categories.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Clinically Significant Vital Signs Abnormalities | SBP (supine) <=95 mmHg and DFB >=20 mmHg | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Vital Signs Abnormalities | SBP (supine) >=160 mmHg and IFB >=20 mmHg | 17 Participants |
| Placebo | Number of Participants With Clinically Significant Vital Signs Abnormalities | DBP (supine) <=45 mmHg and DFB >=10 mmHg | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Vital Signs Abnormalities | DBP (supine) >=110 mmHg and IFB >=10 mmHg | 2 Participants |
| Placebo | Number of Participants With Clinically Significant Vital Signs Abnormalities | HR (supine) <=50 bpm and DFB >= 20 bpm | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Vital Signs Abnormalities | HR (supine) >=120 bpm and IFB >=20 bpm | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Vital Signs Abnormalities | Weight >=5% DFB | 12 Participants |
| Placebo | Number of Participants With Clinically Significant Vital Signs Abnormalities | Weight >=5% IFB | 14 Participants |
| Renvela | Number of Participants With Clinically Significant Vital Signs Abnormalities | Weight >=5% IFB | 9 Participants |
| Renvela | Number of Participants With Clinically Significant Vital Signs Abnormalities | SBP (supine) <=95 mmHg and DFB >=20 mmHg | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Vital Signs Abnormalities | HR (supine) <=50 bpm and DFB >= 20 bpm | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Vital Signs Abnormalities | SBP (supine) >=160 mmHg and IFB >=20 mmHg | 12 Participants |
| Renvela | Number of Participants With Clinically Significant Vital Signs Abnormalities | Weight >=5% DFB | 7 Participants |
| Renvela | Number of Participants With Clinically Significant Vital Signs Abnormalities | DBP (supine) <=45 mmHg and DFB >=10 mmHg | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Vital Signs Abnormalities | HR (supine) >=120 bpm and IFB >=20 bpm | 0 Participants |
| Renvela | Number of Participants With Clinically Significant Vital Signs Abnormalities | DBP (supine) >=110 mmHg and IFB >=10 mmHg | 3 Participants |
Secondary
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.
Time frame: From first dose of IMP to the last dose of IMP +3 days i.e. up to Day 59
Population: Analysis was performed on safety population that consisted of all randomized participants who received at least one dose of IMP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Event | Any TEAE | 86 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Event | Any Treatment emergent SAE | 31 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Event | any TEAE leading to permanent discontinuation | 21 Participants |
| Renvela | Number of Participants With Treatment Emergent Adverse Event | Any TEAE | 83 Participants |
| Renvela | Number of Participants With Treatment Emergent Adverse Event | Any Treatment emergent SAE | 26 Participants |
| Renvela | Number of Participants With Treatment Emergent Adverse Event | any TEAE leading to permanent discontinuation | 12 Participants |
Secondary
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.
Time frame: Week 8
Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Reaching the Target Serum Phosphorus Level (4.6 mg/dL [1.49 mmol/L]) at Week 8 | 6.6 percentage of participants |
| Renvela | Percentage of Participants Reaching the Target Serum Phosphorus Level (4.6 mg/dL [1.49 mmol/L]) at Week 8 | 15.5 percentage of participants |