The COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE

• Sponsor: The Cleveland Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT02258074
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 205
• Locations: 7
• Arms: 4
• Actual Duration (Months): 54
• Patients Per Site: 29.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The COMBINE clinical trial is a pilot study evaluating the effects of nicotinamide and lanthanum carbonate on serum phosphate and fibroblast growth factor 23 (FGF23) in patients with Chronic Kidney Disease (CKD) stages 3-4.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease	Drug: Nicotinamide; Drug: Lanthanum Carbonate; Drug: Placebo (for Nicotinamide); Drug: Placebo (for lanthanum carbonate)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 205 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Other
• Official Title: The COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE
• Actual Study Start Date: Mar 1, 2015
• Actual Primary Completion Date: Nov 1, 2018
• Actual Study Completion Date: Sep 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lanthanum carbonate + nicotinamide One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months.	Drug: Nicotinamide; Drug: Lanthanum Carbonate
Placebo Comparator: Lanthanum carbonate + nicotinamide placebo Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months.	Drug: Lanthanum Carbonate; Drug: Placebo (for Nicotinamide); Sugar pill manufactured to mimic Nicotinamide 750 mg capsule
Active Comparator: Lanthanum carbonate placebo and nicotinamide One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.	Drug: Nicotinamide; Drug: Placebo (for lanthanum carbonate); Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule
Placebo Comparator: Lanthanum carbonate placebo and nicotinamide placebo One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.	Drug: Placebo (for Nicotinamide); Sugar pill manufactured to mimic Nicotinamide 750 mg capsule; Drug: Placebo (for lanthanum carbonate); Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule

Outcome Measures

Primary Outcome Measures

1. FGF23 [Baseline to 12 months]

   Change from baseline to 12 months in FGF23 level.

2. Serum Phosphate (mg/dl) [Baseline to 12 months]

   Change from Baseline to 12 months in serum phosphate level

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients with estimated glomerular filtration rate (eGFR) 20-45 ml/min/1.73m2

2. Age 18-85 years

3. Serum phosphate ≥ 2.8 mg/dL

4. Platelet count ≥ 125,000/mm3

5. Able to provide consent

6. Able to travel to study visits

7. Able to eat at least two meals a day

8. In the opinion of the site investigator, willing and able to follow the study treatment regimen and comply with the site investigator's recommendations.

Exclusion Criteria:

1. History of allergic reaction to nicotinamide, niacin (excluding flushing), multivitamin preparations, or lanthanum carbonate

2. Liver disease, defined as known cirrhosis by imaging or physician diagnosis, documented alcohol use > 14 drinks/week, or aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, or total bilirubin concentrations > 2 times the upper limit of the local laboratory reference range

3. Creatine kinase (CK) concentrations > 2 times the upper limit of the local laboratory reference range

4. Major hemorrhagic event within the past six months requiring in-patient admission

5. Blood or platelet transfusion within the past six months

6. Secondary hyperparathyroidism (PTH > 5 times the upper limit of normal range for the laboratory) or currently taking cinacalcet (Sensipar)

7. Current, clinically significant malabsorption, as determined at the discretion of the site investigator

8. Anemia (screening Hg < 9.0 g/dl)

9. Serum albumin < 2.5 mg/dl

10. Anticipated initiation of dialysis or kidney transplantation within 12 months as assessed by and at the discretion of the site investigator.

11. Use of immunosuppressive medications (stable oral steroids ≤ 10 mg of prednisone/day or inhaled steroids are exempted)

12. In the opinion of the site investigator, active abuse of alcohol or drugs

13. Recent (within the last 14 days) initiation or change in dose of treatment with 1,25 (OH)2 vitamin D or active vitamin D analogues (paricalcitol or hectorol). Patients on stable doses of these agents initiated more than 14 days prior to screening are eligible to participate.

14. Current or recent treatment (within the last 14 days) with phosphate binder or niacin/nicotinamide > 100 mg/day

15. Current participation in another clinical trial or other interventional research

16. Currently taking investigational drugs

17. Institutionalized individuals, including prisoners and nursing home residents

18. Malignancy requiring therapy within 2 years (basal or squamous cell skin carcinoma and localized prostate cancer are exempted)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California at San Diego	San Diego	California	United States	92161
2	Denver Nephrology Research	Denver	Colorado	United States	80230
3	George Washington University	Washington	District of Columbia	United States	20037
4	NorthShore University Health System	Chicago	Illinois	United States	60201
5	Northwestern University	Chicago	Illinois	United States	60611
6	University of Utah	Salt Lake City	Utah	United States	84112
7	Utah VA	Salt Lake City	Utah	United States	84112

Sponsors and Collaborators

• The Cleveland Clinic
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Study Director: Michael F. Flessner, MD, PhD, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Study Director: John W. Kusek, PhD, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Principal Investigator: Jennifer J Gassman, Ph.D., Data Coordinating Center, Cleveland Clinic
• Study Chair: Linda F Fried, MD, University of Pittsburgh

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 22, 2015
• Informed Consent Form - Dec 7, 2015

More Information

Publications

• Isakova T, Ix JH, Sprague SM, Raphael KL, Fried L, Gassman JJ, Raj D, Cheung AK, Kusek JW, Flessner MF, Wolf M, Block GA. Rationale and Approaches to Phosphate and Fibroblast Growth Factor 23 Reduction in CKD. J Am Soc Nephrol. 2015 Oct;26(10):2328-39. doi: 10.1681/ASN.2015020117. Epub 2015 May 12. Review.

• Responsible Party: Jennifer Gassman, PhD, Principal Investigator-Data Coordinating Center, The Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT02258074
• Other Study ID Numbers: DK099877-C; U01DK099877
• First Posted: Oct 7, 2014
• Last Update Posted: Aug 2, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Niacinamide; Niacin; Nicotinic Acids

Study Results

Participant Flow

Arm/Group Title	Lanthanum Carbonate + Nicotinamide	Lanthanum Carbonate + Nicotinamide Placebo	Lanthanum Carbonate Placebo and Nicotinamide	Lanthanum Carbonate Placebo and Nicotinamide Placebo
Arm/Group Description	One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. Nicotinamide Lanthanum Carbonate	Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Lanthanum Carbonate Placebo (for Nicotinamide): Sugar pill manufactured to mimic Nicotinamide 750 mg capsule	One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months. Nicotinamide Placebo (for lanthanum carbonate): Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule	One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months. Placebo (for Nicotinamide): Sugar pill manufactured to mimic Nicotinamide 750 mg capsule Placebo (for lanthanum carbonate): Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule
Period Title: Overall Study
STARTED	53	50	51	51
COMPLETED	52	50	51	51
NOT COMPLETED	1	0	0	0

Baseline Characteristics

Arm/Group Title	Lanthanum Carbonate + Nicotinamide	Lanthanum Carbonate + Nicotinamide Placebo	Lanthanum Carbonate Placebo and Nicotinamide	Lanthanum Carbonate Placebo and Nicotinamide Placebo	Total
Arm/Group Description	One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. Nicotinamide Lanthanum Carbonate	Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Lanthanum Carbonate Placebo (for Nicotinamide): Sugar pill manufactured to mimic Nicotinamide 750 mg capsule	One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months. Nicotinamide Placebo (for lanthanum carbonate): Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule	One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months. Placebo (for Nicotinamide): Sugar pill manufactured to mimic Nicotinamide 750 mg capsule Placebo (for lanthanum carbonate): Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule	Total of all reporting groups
Overall Participants	53	50	51	51	205
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69 (12)	67 (13)	70 (12)	69 (10)	69 (12)
Sex: Female, Male (Count of Participants)
Female	20 37.7%	22 44%	17 33.3%	18 35.3%	77 37.6%
Male	33 62.3%	28 56%	34 66.7%	33 64.7%	128 62.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 9.4%	6 12%	5 9.8%	6 11.8%	22 10.7%
Not Hispanic or Latino	48 90.6%	44 88%	46 90.2%	45 88.2%	183 89.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 2%	1 2%	1 2%	3 1.5%
Asian	4 7.5%	2 4%	3 5.9%	1 2%	10 4.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	13 24.5%	14 28%	9 17.6%	16 31.4%	52 25.4%
White	35 66%	32 64%	37 72.5%	32 62.7%	136 66.3%
More than one race	1 1.9%	0 0%	1 2%	1 2%	3 1.5%
Unknown or Not Reported	0 0%	1 2%	0 0%	0 0%	1 0.5%
Region of Enrollment (participants) [Number]
United States	53 100%	50 100%	51 100%	51 100%	205 100%
Diabetes Mellitus (Count of Participants)
Count of Participants [Participants]	31 58.5%	33 66%	23 45.1%	25 49%	112 54.6%
Systolic BP (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	126.0 (15.0)	129.2 (17.2)	129.7 (15.3)	129.3 (21.2)	128.5 (17.3)
Diastolic BP (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	70.2 (11.1)	71.1 (11.7)	72.0 (12.5)	71.5 (12.8)	71.2 (12.0)
Body Mass Index (kg / m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg / m^2]	33.2 (8.5)	30.9 (6.3)	32.5 (8.1)	31.0 (6.1)	31.9 (7.3)
eGFR ((ml/min/1.73m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [(ml/min/1.73m^2)]	32.2 (7.2)	33.0 (7.9)	32.1 (7.1)	32.3 (7.0)	32.4 (7.3)
Urine Albumin Creatinine Ratio ((g/g) (range is 10th and 90th pctl)) [Median (Full Range) ]
Median (Full Range) [(g/g) (range is 10th and 90th pctl)]	0.1	0.2	0.1	0.2	0.1
Calcitriol Use (Count of Participants)
Count of Participants [Participants]	8 15.1%	10 20%	13 25.5%	10 19.6%	41 20%
Serum Phosphate (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	3.6 (0.5)	3.7 (0.6)	3.8 (0.5)	3.6 (0.5)	3.7 (0.6)
Serum FGF-23 (pg/ml (range is 10th to 90th pctls)) [Median (Full Range) ]
Median (Full Range) [pg/ml (range is 10th to 90th pctls)]	104.0	94.8	103.5	96.4	98.8
Serum Calcium (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	9.5 (0.5)	9.5 (0.5)	9.5 (0.5)	9.5 (0.5)	9.5 (0.5)
Intact PTH (pg/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pg/ml]	121.4 (88.7)	123.2 (75.8)	115.6 (80.4)	124.6 (94.7)	121.2 (84.8)
Urine Phosphorus (mg/24 hrs) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/24 hrs]	657.4 (265.2)	658.5 (267.9)	712.8 (235.0)	644.4 (245.2)	668.1 (252.9)
Phosphorus/Creatinine Ratio (mg/g) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/g]	447.0 (146.1)	451.6 (120.9)	487.4 (126.4)	462.9 (130.7)	462.1 (131.5)

Outcome Measures

1. Primary Outcome

Title	FGF23
Description	Change from baseline to 12 months in FGF23 level.
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

Adults with CKD

Arm/Group Title	Lanthanum Carbonate + Nicotinamide	Lanthanum Carbonate + Nicotinamide Placebo	Lanthanum Carbonate Placebo and Nicotinamide	Lanthanum Carbonate Placebo and Nicotinamide Placebo
Arm/Group Description	One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. Nicotinamide Lanthanum Carbonate	Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Lanthanum Carbonate Placebo (for Nicotinamide): Sugar pill manufactured to mimic Nicotinamide 750 mg capsule	One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months. Nicotinamide Placebo (for lanthanum carbonate): Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule	One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months. Placebo (for Nicotinamide): Sugar pill manufactured to mimic Nicotinamide 750 mg capsule Placebo (for lanthanum carbonate): Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule
Measure Participants	53	50	51	51
Mean (95% Confidence Interval) [pg/ml]	.047	-.003	.193	.138

2. Primary Outcome

Title	Serum Phosphate (mg/dl)
Description	Change from Baseline to 12 months in serum phosphate level
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lanthanum Carbonate + Nicotinamide	Lanthanum Carbonate + Nicotinamide Placebo	Lanthanum Carbonate Placebo and Nicotinamide	Lanthanum Carbonate Placebo and Nicotinamide Placebo
Arm/Group Description	One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. Nicotinamide Lanthanum Carbonate	Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Lanthanum Carbonate Placebo (for Nicotinamide): Sugar pill manufactured to mimic Nicotinamide 750 mg capsule	One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months. Nicotinamide Placebo (for lanthanum carbonate): Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule	One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months. Placebo (for Nicotinamide): Sugar pill manufactured to mimic Nicotinamide 750 mg capsule Placebo (for lanthanum carbonate): Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule
Measure Participants	53	50	51	51
Mean (95% Confidence Interval) [mg/dl]	0.06	0.06	0.12	0.12

Adverse Events

Time Frame	1 year
Arm/Group Title	Lanthanum Carbonate + Nicotinamide		Lanthanum Carbonate + Nicotinamide Placebo		Lanthanum Carbonate Placebo and Nicotinamide		Lanthanum Carbonate Placebo and Nicotinamide Placebo
Arm/Group Description	One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. Nicotinamide Lanthanum Carbonate		Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Lanthanum Carbonate Placebo (for Nicotinamide): Sugar pill manufactured to mimic Nicotinamide 750 mg capsule		One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months. Nicotinamide Placebo (for lanthanum carbonate): Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule		One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months. Placebo (for Nicotinamide): Sugar pill manufactured to mimic Nicotinamide 750 mg capsule Placebo (for lanthanum carbonate): Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule
All Cause Mortality
	Lanthanum Carbonate + Nicotinamide		Lanthanum Carbonate + Nicotinamide Placebo		Lanthanum Carbonate Placebo and Nicotinamide		Lanthanum Carbonate Placebo and Nicotinamide Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/53 (1.9%)		0/50 (0%)		1/51 (2%)		1/51 (2%)
Serious Adverse Events
	Lanthanum Carbonate + Nicotinamide		Lanthanum Carbonate + Nicotinamide Placebo		Lanthanum Carbonate Placebo and Nicotinamide		Lanthanum Carbonate Placebo and Nicotinamide Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/53 (34%)		14/50 (28%)		14/51 (27.5%)		14/51 (27.5%)
Cardiac disorders
Cardiovascular Hospitalizations	8/53 (15.1%)	12	4/50 (8%)	5	4/51 (7.8%)	6	6/51 (11.8%)	12
Endocrine disorders
Endocrine	1/53 (1.9%)	1	0/50 (0%)	0	1/51 (2%)	2	2/51 (3.9%)	2
Gastrointestinal disorders
GI Hospitalizations	2/53 (3.8%)	2	5/50 (10%)	5	1/51 (2%)	1	0/51 (0%)	0
Hepatobiliary disorders
Hepatic Hospitalizations	1/53 (1.9%)	1	0/50 (0%)	0	0/51 (0%)	0	0/51 (0%)	0
Infections and infestations
Infection-related Hospitalizations	3/53 (5.7%)	3	3/50 (6%)	3	3/51 (5.9%)	3	1/51 (2%)	1
Injury, poisoning and procedural complications
Injury	0/53 (0%)	0	0/50 (0%)	0	1/51 (2%)	1	0/51 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal	1/53 (1.9%)	1	1/50 (2%)	1	2/51 (3.9%)	2	1/51 (2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignancy	2/53 (3.8%)	2	1/50 (2%)	1	0/51 (0%)	0	0/51 (0%)	0
Nervous system disorders
Nervous System	2/53 (3.8%)	2	0/50 (0%)	0	1/51 (2%)	1	2/51 (3.9%)	2
Renal and urinary disorders
Reached ESRD (dialysis or transplant)	4/53 (7.5%)	4	1/50 (2%)	1	2/51 (3.9%)	2	1/51 (2%)	1
Renal Hospitalizations	5/53 (9.4%)	5	2/50 (4%)	2	1/51 (2%)	1	3/51 (5.9%)	3
Respiratory, thoracic and mediastinal disorders
Respiratory	3/53 (5.7%)	3	0/50 (0%)	0	0/51 (0%)	0	0/51 (0%)	0
Surgical and medical procedures
Surgical and Medical Procedures	0/53 (0%)	0	0/50 (0%)	0	1/51 (2%)	1	0/51 (0%)	0
Other (Not Including Serious) Adverse Events
	Lanthanum Carbonate + Nicotinamide		Lanthanum Carbonate + Nicotinamide Placebo		Lanthanum Carbonate Placebo and Nicotinamide		Lanthanum Carbonate Placebo and Nicotinamide Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/53 (62.3%)		29/50 (58%)		30/51 (58.8%)		26/51 (51%)
Blood and lymphatic system disorders
Bruising	20/53 (37.7%)	57	16/50 (32%)	32	21/51 (41.2%)	55	18/51 (35.3%)	47
Bleeding	10/53 (18.9%)	18	13/50 (26%)	21	10/51 (19.6%)	22	7/51 (13.7%)	14
Platelets < 100,000	1/53 (1.9%)	2	0/50 (0%)	0	0/51 (0%)	0	2/51 (3.9%)	4
Cardiac disorders
Creatine Kinase > 800 U/L	1/53 (1.9%)	1	0/50 (0%)	0	0/51 (0%)	0	0/51 (0%)	0
Gastrointestinal disorders
Nausea (severe)	11/53 (20.8%)	20	9/50 (18%)	15	4/51 (7.8%)	9	4/51 (7.8%)	4
Heartburn (severe)	2/53 (3.8%)	3	3/50 (6%)	5	0/51 (0%)	0	4/51 (7.8%)	6
Diarrhea (severe)	12/53 (22.6%)	22	5/50 (10%)	8	8/51 (15.7%)	14	7/51 (13.7%)	15
Hepatobiliary disorders
Liver Function Abnormalities	0/53 (0%)	0	0/50 (0%)	0	0/51 (0%)	0	0/51 (0%)	0
Immune system disorders
Hives	1/53 (1.9%)	3	5/50 (10%)	5	9/51 (17.6%)	13	0/51 (0%)	0
Renal and urinary disorders
Serum Phosphate >= 5.9 mg/dl	1/53 (1.9%)	2	1/50 (2%)	1	0/51 (0%)	0	0/51 (0%)	0
Serum Phosphate < 1.5 mg/dl	1/53 (1.9%)	1	0/50 (0%)	0	0/51 (0%)	0	0/51 (0%)	0
Skin and subcutaneous tissue disorders
Flushing	1/53 (1.9%)	1	5/50 (10%)	14	4/51 (7.8%)	7	4/51 (7.8%)	8

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.