Chewed vs. Crushed Lanthanum Carbonate in Hemodialysis Patients

• Sponsor: University of Illinois at Chicago (Other)
• Overall Status: Completed
• CT.gov ID: NCT00660530
• Collaborator: Shire (Industry)
• Enrollment: 11
• Location: 1
• Arms: 2
• Duration (Months): 22
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Patients with end-stage renal disease (ESRD) commonly develop hyperphosphatemia due to the loss of excretory function of the kidney. This in turn may lead to the development of secondary hyperparathyroidism (SHPT) and renal osteodystrophy. Lanthanum carbonate, a phosphate binding agent, works by releasing lanthanum ions in the gastrointestinal tract to bind dietary phosphate and is effective in the management of hyperphosphatemia and in preventing secondary hyperparathyroidism.

Patients taking lanthanum carbonate as part of their phosphate binder therapy are counseled to chew the tablets completely before swallowing, with or immediately after meals. However, ESRD patients who are intubated or are receiving enteral tube feedings are unable to chew the lanthanum carbonate tablets. For such patients, medications are commonly crushed and administered through a gastrostomy tube (G-tube). Some patients may also prefer to crush the lanthanum carbonate tablets and mix it with food instead of chewing. To date, it is not known if crushing the lanthanum carbonate tablets prior to administration and taking it with food will be as efficacious as chewing it.

The objective of this study is to compare the efficacy of phosphate binding between chewed and crushed lanthanum carbonate in patients undergoing hemodialysis.

Condition or Disease	Intervention/Treatment	Phase
Hyperphosphatemia; Kidney Disease	Drug: Lanthanum Carbonate Chewable Product; Drug: Lanthanum carbonate crushed powder	Phase 2

Detailed Description

Study subjects Men and women at least 18 years of age, receiving HD for at least 3 months, with serum P concentrations 45.5 mg/dL at the end of the washout period, and on a stable dose of P binder and/or active vitamin D (if prescribed previously) for at least 1 month before the study were eligible for study participation. Patients were excluded if they did not respond to P binder therapy previously, had a known noncompliance with oral medications (e.g., failure to fill a prescription or to take medications as prescribed), severe hyperparathyroidism defined as intact-PTH (i-PTH) 4500 pg/mL, were taking any calcium (Ca)-, magnesium-, or aluminum-containing antacids or used an investigational agent within 30 days of study entry.

Study design This study was approved by the University of Illinois at Chicago Institutional Review Board. Informed consent was obtained from the subjects before any study procedures were initiated. One week before the administration of crushed or chewed lanthanum, the subjects were in-structed to discontinue their P-binding agents (calcium carbonate, calcium acetate, sevelamer hydrochloride, and/or lanthanum carbonate), if prescribed previously. At the end of the 1-week washout period, subjects whose serum P exceeded 5.5 mg/dL were randomized to receive, in a crossover fashion, lanthanum 1000 mg (Fosrenol, Shire US Inc., Wayne, PA, USA) 3 times daily to be chewed with meals (chewed LAN) or lanthanum 1000 mg crushed into a fine powder and taken with meals 3 times daily (crushed LAN), for 4 weeks each. The lanthanum tablets were crushed into a fine powder using a mortar and pestle by the investigators, individually wrapped in powder packets and dispensed to the subjects on a weekly basis. The subjects were instructed to empty the powder into a small plastic cup provided, mix with 2 tablespoonfuls of applesauce and take it with meals. After each treatment (chewed or crushed LAN), there was a 1-week washout period.

Throughout the course of the study, the subjects were asked to keep a constant dietary P intake. In addition, each subject was provided with a dietary log for recording their daily dietary intake.

Sample collection and study endpoints Blood samples were collected at the end of each washout period (baseline) and weekly (weeks 1-4) during lanthanum treatment for the determination of serum P, Ca, i-PTH, and albumin (alb) concentrations. Changes in serum P from baseline for crushed and chewed lanthanum were compared. In addition, the study subjects were asked to complete a questionnaire to assess the presence of any study-related adverse events at the end of each treatment arm.

Statistical considerations Assuming a coefficient variation of 15% to 25% for serum P concentrations, a sample size of 11 to 15 was estimated to provide at least 80% power to detect a 25% difference in serum P between study treatments, using a 2-sided test and a of 0.05. Statistical analyses were performed using PASW (SPSS), version 17.0 (Chicago, IL, USA). Descriptive statistics were used to report all results. The changes in serum P, Ca, i-PTH, and alb were compared between the 2 treatment arms using paired sample t test. A P value <0.05 was considered statistically significant.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Evaluation of Chewed vs. Crushed Lanthanum Carbonate in the Efficacy of Phosphate Binding in Hemodialysis Patients
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 One week before the administration of crushed or chewed lanthanum, the subjects were instructed to discontinue their P-binding agents, if prescribed previously. At the end of the 1-week washout period, subjects whose serum P exceeded 5.5 mg/dL were randomized to receive, in a crossover fashion, lanthanum 1000 mg (Fosrenol, Shire US Inc., Wayne, PA, USA) 3 times daily to be chewed with meals (chewed LAN) or lanthanum 1000 mg crushed into a fine powder and taken with meals 3 times daily (crushed LAN), for 4 weeks each. The lanthanum tablets were crushed into a fine powder using a mortar and pestle by the investigators, individually wrapped in powder packets and dispensed to the subjects on a weekly basis. The subjects were instructed to empty the powder into a small plastic cup provided, mix with 2 tablespoonfuls of applesauce and take it with meals. After each treatment (chewed or crushed LAN), there was a 1-week washout period.	Drug: Lanthanum Carbonate Chewable Product; Lanthanum carbonate 1 g to be chewed, three times daily with meals; Other Names: Fosrenol
Experimental: 2 After the one-week washout period, the subject received the other lanthanum treatment (chewed or crushed) that they did not receive in the initial treatment period.	Drug: Lanthanum carbonate crushed powder; Lanthanum carbonate (Fosrenol) 1 g crushed into a fine powder, three times daily with meal; Other Names: Fosrenol

Outcome Measures

Primary Outcome Measures

1. Serum Phosphorous Concentration [Week 1-4 mean]

   measure of serum P concentration

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male or female 18 years of age or older

• Have been on hemodialysis for at least 3 months

• Women of child-bearing potential (premenopausal and not surgically sterilized) who have a negative serum pregnancy test

• On a stable dose of phosphate binder for at least 1 month prior to the study

• On a stable dose of active vitamin D (if previously prescribed) for at least 1 month prior to the study

• Serum phosphorus concentrations > 5.5 mg/dL (1.78 mmol/L) at the end of the washout period

Exclusion Criteria:

• Did not previously respond to phosphate binder therapy

• Known non-compliance with oral medications

• Severe hyperparathyroidism defined as intact-PTH (i-PTH) > 500 pg/ml

• Taking any calcium-, magnesium- or aluminum-containing antacids

• Use of an investigational agent within 30 days of study entry

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Illinois at Chicago	Chicago	Illinois	United States	60612

Sponsors and Collaborators

• University of Illinois at Chicago
• Shire

Investigators

• Principal Investigator: Alan H Lau, Pharm.D., Univsersity of Illinois at Chicago

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alan Lau, Professor, University of Illinois at Chicago
• ClinicalTrials.gov Identifier: NCT00660530
• Other Study ID Numbers: 2006-0588
• First Posted: Apr 17, 2008
• Last Update Posted: Nov 3, 2020
• Last Verified: Oct 1, 2020

• Keywords provided by Alan Lau, Professor, University of Illinois at Chicago: stage 5; chronic; hemodialysis
• Additional relevant MeSH terms: Kidney Diseases; Hyperphosphatemia

Study Results

Participant Flow

Recruitment Details	Men and women at least 18 years of age, receiving hemodialysis (HD) for at least 3 months, with serum P concentrations > 5.5 mg/dL at the end of the washout period, and on a stable dose of P binder and/or active vitamin D (if previously prescribed) for at least 1 month prior to the study were eligible for study participation.
Pre-assignment Detail	Patients were excluded if they did not previously respond to P binder therapy, had a known non-compliance with oral medications, severe hyperparathyroidism defined as intact-PTH (i-PTH) > 500 pg/ml, were taking any calcium-, magnesium- or aluminum-containing antacids or used an investigational agent within 30 days of study entry.

Arm/Group Title	Chewed or Crushed Lanthanum Carbonate
Arm/Group Description	Lanthanum carbonate 1 g to be chewed or crushed, three times daily with meals, after 1-week washout period, then Lanthanum carbonate 1 g to be chewed crushed, three times daily with meals (the treatment that the subject did not receive in the initial treatment).
Period Title: Overall Study
STARTED	11
COMPLETED	11
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Chewed or Crushed Lanthanum Carbonate
Arm/Group Description	Lanthanum carbonate 1 g to be chewed or crushed, three times daily with meals
Overall Participants	11
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	9 81.8%
>=65 years	2 18.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55 (13.7)
Sex: Female, Male (Count of Participants)
Female	4 36.4%
Male	7 63.6%
Region of Enrollment (participants) [Number]
United States	11 100%

Outcome Measures

1. Primary Outcome

Title	Serum Phosphorous Concentration
Description	measure of serum P concentration
Time Frame	Week 1-4 mean

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chewed Lanthanum Carbonate	Crushed Lanthanum Carbonate
Arm/Group Description	Lanthanum carbonate 1 g to be chewed, three times daily with meals	Lanthanum carbonate 1 g crushed into a fine powder, three times daily with meal Lanthanum carbonate: Lanthanum carbonate 1 g crushed into a fine powder, three times daily with meal
Measure Participants	11	11
Mean (Standard Error) [mg/dL]	2.0 (0.5)	1.7 (0.4)

Adverse Events

Time Frame	4 weeks for each cross-over period
Adverse Event Reporting Description	non-systematic assessment
Arm/Group Title	Chewed Lanthanum Carbonate		Crushed Lanthanum Carbonate
Arm/Group Description	Lanthanum carbonate 1 g to be chewed, three times daily with meals		Lanthanum carbonate 1 g crushed into a fine powder, three times daily with meal
All Cause Mortality
	Chewed Lanthanum Carbonate		Crushed Lanthanum Carbonate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Chewed Lanthanum Carbonate		Crushed Lanthanum Carbonate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/11 (9.1%)		2/11 (18.2%)
Gastrointestinal disorders
Severe Constipation	1/11 (9.1%)	1	1/11 (9.1%)	1
Severe Diarrhea	0/11 (0%)	0	1/11 (9.1%)	1
Other (Not Including Serious) Adverse Events
	Chewed Lanthanum Carbonate		Crushed Lanthanum Carbonate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/11 (63.6%)		6/11 (54.5%)
Gastrointestinal disorders
Nausea	2/11 (18.2%)	2	2/11 (18.2%)	2
Vomiting	0/11 (0%)	0	1/11 (9.1%)	1
Constipation	1/11 (9.1%)	1	0/11 (0%)	0
Diarrhea	0/11 (0%)	0	0/11 (0%)	0
Abdominal distension	2/11 (18.2%)	2	1/11 (9.1%)	1
Abdominal pain	1/11 (9.1%)	1	1/11 (9.1%)	1
Vascular disorders
Dizziness	1/11 (9.1%)	1	1/11 (9.1%)	1

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.