The Pharmacokinetics of Rocaltrol When Administered Alone or in Combination With Fosrenol or Renvela in Healthy Volunteers

Study Overview
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Brief Summary
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To assess the effects of lanthanum carbonate (FOSRENOL) or sevelamer carbonate (RENVELA) on the pharmacokinetics of oral calcitriol (ROCALTROL)

Official Title
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A Phase I, Randomized, Open-Label, Three Period Cross-Over Study to Assess the Pharmacokinetics of Oral Calcitriol (ROCALTROL®) in Healthy Volunteers When Administered Alone or When Co-Administered With Lanthanum Carbonate (FOSRENOL®) or Sevelamer Carbonate (RENVELA®)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Calcitriol
* Drug: Lanthanum carbonate + Calcitriol
* Drug: Sevelamer carbonate + Calcitriol


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Healthy volunteers age 19-45 years inclusive at the time of consent. Satisfactory medical assessment with no clinically significant or relevant abnormalities in medical history, physical examination, vital signs, electrocardiogram (ECG) and laboratory evaluation (hematology, biochemistry, urinalysis) as assessed by the Investigator. No current or recurrent disease (e.g. cardiovascular, renal, liver, gastrointestinal (GI), malignancy or other conditions) that could affect the action, absorption or disposition of the investigational products utilized in this study, or could affect clinical or laboratory assessments. Exclusion criteria Current or recurrent disease (eg, cardiovascular, renal, liver, GI, malignancy or other conditions) that could affect the action, absorption or disposition of the investigational products utilized in this study, or could affect clinical or laboratory assessments. Current or relevant previous of physical or psychiatric illness, any medical disorder that could have required treatment or made the subject unlikely to fully complete the study, or any condition that presented undue risk from the investigational product or study procedures. Current use of any medication with the exception of hormonal replacement therapy or hormonal contraceptives within 14 days of first dose of investigational product. History of alcohol or other substance abuse within the last year. A positive human immunodeficiency virus antibody screen, Hepatitis B surface antigen or Hepatitis C virus antibody screen. Use of tobacco in any form Donation of blood or blood products (eg, plasma or platelets) within 60 days prior to receiving the first dose of investigational product.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Calcitriol<br> | Drug: Calcitriol<br>* Calcitriol (1.0 microgram) single dose at lunch administered on Day 1 of the study period.<br>* Other names: Rocaltrol;|
| Experimental: Lanthanum carbonate + calcitriol<br> | Drug: Lanthanum carbonate + Calcitriol<br>* Lanthanum carbonate (1000 mg three times daily with meals for one day) + calcitriol (1.0 microgram) single dose at lunch administered on Day 1 of the study period.<br>* Other names: Fosrenol + Rocaltrol;|
| Experimental: Sevelamer carbonate + calcitriol<br> | Drug: Sevelamer carbonate + Calcitriol<br>* Sevelamer carbonate (2400 mg three times daily with meals for one day) + calcitriol (1.0 microgram) single dose at lunch administered on Day 1 of the study period.<br>* Other names: Renvela + Rocaltrol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Serum Concentration-time Curve (AUC 0-48) for Exogenous Calcitriol | This shows the effect that lanthanum carbonate or sevelamer carbonate has on the pharmacokinetics of oral calcitriol. Exogenous calcitriol was the difference between total calcitriol value and the baseline exogenous calcitriol value at each sampling timepoint. | pre-dose, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hours post calcitriol dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) for Exogenous Calcitriol | This shows the effect that lanthanum carbonate or sevelamer carbonate has on the pharmacokinetics of oral calcitriol. Exogenous calcitriol was the difference between total calcitriol value and the baseline exogenous calcitriol value at each sampling timepoint. | pre-dose, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hours post calcitriol dose | 
| Time of Maximum Plasma Concentration (Tmax) for Exogenous Calcitriol | This shows the effect that lanthanum carbonate or sevelamer carbonate has on the pharmacokinetics of oral calcitriol. Exogenous calcitriol was the difference between total calcitriol value and the baseline exogenous calcitriol value at each sampling timepoint. | pre-dose, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hours post calcitriol dose |