Pharmacodynamic Study of Two Lanthanum Carbonate Formulations in Healthy Adults

Study Overview
=================
Brief Summary
-----------------
This study is being conducted to assess any potential differences in the absorption and excretion between two lanthanum carbonate formulations. This study is also being done to assess the safety and tolerability of the two lanthanum carbonate formulations.

Official Title
-----------------
A Phase I Pharmacodynamic Equivalence Study Comparing Urinary Phosphate Excretion and Plasma Lanthanum Pharmacokinetics for a Lanthanum Carbonate Granule Formulation and Chewable Tablets Administered to Healthy Adult Subjects

Conditions
-----------------
End Stage Renal Disease

Intervention / Treatment
-----------------
* Drug: Lanthanum carbonate Granule Formulation
* Drug: Lanthanum carbonate Chewable Tablets (Fosrenol)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Ability to provide informed consent to participate in the study. Healthy volunteers, age 18-55 inclusive. Subject must be willing to comply with applicable contraceptive requirements of the protocol Female subjects must have a negative pregnancy test Ability to chew and or swallow doses of the investigational products as prescribed in the protocol. Ability to fully comply with all study procedures and restrictions, including consumption of all food provided while a resident in the CRC. Exclusion Criteria Current or relevant previous history of physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or study procedures. Clinically significant abnormal serum phosphate levels, outside of normal limits. Current use of any medication with the exception of hormonal replacement therapy or hormonal contraceptives within 7 days of first dose of investigational product. A known history of lactose intolerance or allergy to milk or other foods. Clinically significant or multiple allergies as determined by an Investigator. History of alcohol or other substance abuse within the last 6 months. A positive screen for alcohol or drugs of abuse. Male subjects who consume more than 21 units of alcohol per week or three units per day. Female subjects who consume more than 14 units of alcohol per week or two units per day. A positive human immunodeficiency virus (HIV) antibody screen, Hepatitis B surface antigen (HBsAg) or Hepatitis C virus (HCV) antibody screen. Female subjects who are pregnant (positive pregnancy test), lactating, or less than 90 days post-partum. Subjects that have previously been randomized in this study. Use of tobacco in any form or other nicotine-containing products in any form. Ex-users must report that they have stopped using tobacco for at least 60 days prior to receiving the first dose of investigational product. Routine consumption of more than two units of caffeine per day or subjects who experience caffeine withdrawal headaches. Donation of blood or blood products within 60 days prior to receiving the first dose of investigational product. Plasma donation within 28 days prior to the first dose of the investigational product. Use of another investigational product within 30 days prior to receiving the first dose of investigational product or active enrolment in another drug or vaccine clinical study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lanthanum carbonate granules<br>Lanthanum carbonate granulated formulation crossover to chewable tablet formulation | Drug: Lanthanum carbonate Granule Formulation<br>* 3x's per day for 3 days, 1 dose in the am for day 4. (A single dose equals 1000mg of lanthanum carbonate granule formulation. Dose is administered immediately after each meal.)<br>|
| Experimental: Lanthanum carbonate chewable tablets (Fosrenol)<br>Lanthanum carbonate chewable table formulation crossover to granulated formulation | Drug: Lanthanum carbonate Chewable Tablets (Fosrenol)<br>* 3x's per day for 3 days, 1 dose on day 4. (A single dose equals a 1000mg tablet of lanthanum carbonate. Dose is administered immediately after each meal.)<br>* Other names: Fosrenol;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary Phosphate Excretion 3-Day Average |  | Continuous collection over 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary Phosphate Excretion on Day 4 |  | Continuous collection on Day 4 | 
| Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Lanthanum Carbonate |  | 3, 4, 5, 6, 8, 12, 18, 24, 36 and 48 hours post-dose on Day 4 | 
| Maximum Plasma Concentration (Cmax) of Lanthanum Carbonate |  | 3, 4, 5, 6, 8, 12, 18, 24, 36 and 48 hours post-dose on Day 4 | 
| Time of Maximum Plasma Concentration (Tmax) of Lanthanum Carbonate |  | 3, 4, 5, 6, 8, 12, 18, 24, 36 and 48 hours post-dose on Day 4 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
End stage Renal disease