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

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®)

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Calcitriol; Drug: Lanthanum carbonate + Calcitriol; Drug: Sevelamer carbonate + Calcitriol

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630
      • West Coast Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Calcitriol	Drug: Calcitriol; Calcitriol (1.0 microgram) single dose at lunch administered on Day 1 of the study period.; Other Names: Rocaltrol
Experimental: Lanthanum carbonate + calcitriol	Drug: Lanthanum carbonate + Calcitriol; 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.; Other Names: Fosrenol + Rocaltrol
Experimental: Sevelamer carbonate + calcitriol	Drug: Sevelamer carbonate + Calcitriol; 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.; Other Names: Renvela + Rocaltrol

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Pierce D, Hossack S, Poole L, Robinson A, Van Heusen H, Martin P, Smyth M. The effect of sevelamer carbonate and lanthanum carbonate on the pharmacokinetics of oral calcitriol. Nephrol Dial Transplant. 2011 May;26(5):1615-21. doi: 10.1093/ndt/gfq598. Epub 2010 Oct 4.

Helpful Links

• FDA Recall Information

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2009
• Primary Completion (Actual): July 31, 2009
• Study Completion (Actual): July 31, 2009

Study Registration Dates

• First Submitted: June 19, 2009
• First Submitted That Met QC Criteria: June 19, 2009
• First Posted (Estimate): June 22, 2009

Study Record Updates

• Last Update Posted (Actual): June 15, 2021
• Last Update Submitted That Met QC Criteria: May 27, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Micronutrients; Membrane Transport Modulators; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Chelating Agents; Sequestering Agents; Vasoconstrictor Agents; Calcium Channel Agonists; Sevelamer; Calcitriol
• Other Study ID Numbers: SPD405-129