Bioequivalence Study of BAY 77-1931 Orally Disintegrating Tablet

Study Overview
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Brief Summary
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The primary objective of this study was to establish the bioequivalence of two different tablet formulations containing BAY77-1931. The secondary objectives of this study were to assess the safety and tolerability, as well as to Investigate the plasma lanthanum concentration after BAY 77-1931 ODT 500 mg administration.

Official Title
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Bioequivalence Study of BAY 77-1931 Orally Disintegrating Tablet - Randomized, Open-label, Two-way Crossover Study to Establish the Bioequivalence Between BAY 77-1931 Orally Disintegrating Tablet 500 mg and Fosrenol Chewable Tablet 500 mg Administered in Japanese Healthy Male Adult Subjects

Conditions
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Clinical Pharmacology

Intervention / Treatment
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* Drug: Fosrenol ODT (Lanthanum Carbonate, BAY77-1931)
* Drug: Fosrenol chewable Tablet (Lanthanum Carbonate, BAY77-1931)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese healthy male adult volunteers (age, 20-45 years; BMI, 17.6-26.4 kg/m2) Exclusion Criteria: Regular use of medicines including Chinese herbal drugs Clinically relevant findings in the physical examination Subject who cannot take the study drug appropriately (e.g. weak biting force, insufficient salivary flow)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fosrenol ODT (Lanthanum Carbonate, BAY77-1931)<br>Fosrenol BAY 77-1931 orally disintegrating tablet (ODT) 500 mg in Period 1 (day 1-3) and Fosrenol chewable tablet 500mg in Period 2 (day 4-6). The washout interval between period 1 and 2 will be at least 14 days. | Drug: Fosrenol ODT (Lanthanum Carbonate, BAY77-1931)<br>* Fosrenol orally disintegrating tablet, ODT (Lanthanum Carbonate, BAY77-1931) 500 mg, TID<br>|
| Active Comparator: Fosrenol chewable Tablet (Lanthanum Carbonate, BAY77-1931)<br>Fosrenol BAY77-1931 chewable tablet in Period 1 and Fosrenol BAY 77-1931 ODT 500 mg in Period 2. The washout interval between period 1 and 2 will be at least 14 days. | Drug: Fosrenol chewable Tablet (Lanthanum Carbonate, BAY77-1931)<br>* Fosrenol chewable Tablet (Lanthanum Carbonate, BAY77-1931) 500mg, TID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics: Daily urinary phosphate excretion (mmol) on each day | Each study drug was administered as multiple dose over 4-days under fed conditions with a washout interval of at least 14 days in between. Twenty four hours urine collection were repeated 5 times from morning on Day -2 to that on Day 4. | 6 days | 
| Bioequivalence: Average of daily urinary phosphate excretion (mmol) over 3-day dosing period | During lanthanum carbonate TID treatment period over 3 days in each period (period 1 = day 1-3; period 2 = day 4-6) | baseline and over 3-days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics: Daily urinary phosphate excretion (mmol) on Day 3 |  | 1 day | 
| Plasma lanthanum concentrations (ng/mL) | To measure plasma concentration of lanthanum, 6 mL of blood were collected before the breakfast on Day 1, Day 2, Day 3 and Day 4, and at 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36 and 48 hours after administration on Day 4. | 6 days | 
| Pharmacokinetics: Cmax,md of lanthanum in plasma from pre-administration (Day 4) to 48 hours after the last administration (Day 6) |  | 6 days | 
| Pharmacokinetics: tmax,md of lanthanum in plasma from pre-administration (Day 4) to 48 hours after the last administration (Day 6) |  | 6 days | 
| Pharmacokinetics: Cmax,md,norm of lanthanum in plasma from pre-administration (Day 4) to 48 hours after the last administration (Day 6) |  | 6 days | 
| Pharmacokinetics: AUC(0-tlast)md,norm of lanthanum in plasma from pre-administration (Day 4) to 48 hours after the last administration (Day 6) |  | 6 days | 
| Pharmacokinetics: t1/2,md of lanthanum in plasmafrom pre-administration (Day 4) to 48 hours after the last administration (Day 6) |  | 6 days | 
| Number of adverse events as a measure of safety and tolarability |  | From Day 1, the day of the first study drug administration, in period 1 (day 1-3) to follow up, 7-10 days after the last study drug administration in period 2 (day 4 - 6) | 
| Pharmacokinetics: AUC(0-tlast)md of lanthanum in plasma from pre-administration (Day 4) to 48 hours after the last administration (Day 6) |  | 6 days |