Clinical Trial: Study of rhPTH(1-84) in Japanese Healthy Subjects Compared With Matched Caucasian Healthy Adult Subjects

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase 1, Open-label, Randomized, Cross-over Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of a Single Dose of rhPTH(1-84) Administered Subcutaneously in Japanese Healthy Subjects

Brief Summary: The purpose of this study is to compare how the body handles rhPTH(1-84) and how rhPTH(1-84) affects the body between healthy adults of Japanese descent and matched, healthy Caucasian adults.

Detailed Summary:
Sponsor: Shire

Current Primary Outcome:

  • Maximum Observed Drug Concentration (Cmax) of rhPTH(1-84) in Plasma [ Time Frame: NHC:30 and 90 minutes (mins) PRD, 10,20,30,45 mins, 1,1.25,1.5,2,2.5,3,4,6,8,12,16 hours (h) (Day 1), 24 h (Day 2) JD: 30 and 90 mins PRD, 10,20,30,45 mins, 1,1.25,1.5,2,2.5,3,4,6,8,12,16 h (Days 1,4,7),24 h (Days 2,5,8) ]
    Maximum concentration occurring at time of maximum observed concentration (total and baseline adjusted) of rhPTH(1-84) administered as a single subcutaneous (SC) dose of 100 microgram (mcg) in plasma during a dosing interval between healthy adult volunteer subjects of Japanese descent and matched, non-Hispanic, healthy, adult Caucasian subjects. Pharmacokinetic (PK) parameters will be calculated from original and baseline-adjusted plasma concentration-time data using noncompartmental methods and all calculations will be based on actual sampling times. Here NHC refers to Non-Hispanic Caucasians and JD refers to Japanese Descents. PRD refers to predose.
  • Time to Reach Maximum Observed Drug Concentration (Tmax) of rhPTH(1-84) in Plasma [ Time Frame: NHC:30 and 90 mins PRD, 10,20,30,45 mins, 1,1.25,1.5,2,2.5,3,4,6,8,12,16 h (Day 1), 24 h (Day 2) JD: 30 and 90 mins PRD, 10,20,30,45 mins, 1,1.25,1.5,2,2.5,3,4,6,8,12,16 h (Days 1,4,7),24 h (Days 2,5,8) ]
    Time to reach maximum observed drug concentration of rhPTH(1-84) administered as a single SC dose of 100 mcg in plasma during a dosing interval between healthy adult volunteer subjects of Japanese descent and matched, non-Hispanic, healthy, adult Caucasian subjects. PK parameters will be calculated from original and baseline-adjusted plasma concentration-time data using noncompartmental methods and all calculations will be based on actual sampling times. Here NHC refers to Non-Hispanic C

    Original Primary Outcome:

    • Maximum Observed Drug Concentration (Cmax) of rhPTH(1-84) in Plasma [ Time Frame: NHC:30 and 90 minutes (mins) PRD, 10,20,30,45 mins, 1,1.25,1.5,2,2.5,3,4,6,8,12,16 hours (h) (Day 1), 24 h (hours) (Day 2) JD: 30 and 90 mins PRD, 10,20,30,45 mins, 1,1.25,1.5,2,2.5,3,4,6,8,12,16 h (Days 1,4,7),24 h (Days 2,5,8) ]
      Maximum concentration occurring at time of maximum observed concentration (total and baseline adjusted) of rhPTH(1-84) administered as a single subcutaneous (SC) dose of 100 microgram (mcg) in plasma during a dosing interval between healthy adult volunteer subjects of Japanese descent and matched, non-Hispanic, healthy, adult Caucasian subjects. Pharmacokinetic (PK) parameters will be calculated from original and baseline-adjusted plasma concentration-time data using noncompartmental methods and all calculations will be based on actual sampling times. Here NHC refers to Non-Hispanic Caucasians and JD refers to Japanese Descents. PRD refers to predose.
    • Time to Reach Maximum Observed Drug Concentration (Tmax) of rhPTH(1-84) in Plasma [ Time Frame: NHC:30 and 90 mins PRD, 10,20,30,45 mins, 1,1.25,1.5,2,2.5,3,4,6,8,12,16 h (Day 1), 24 h (Day 2) JD: 30 and 90 mins PRD, 10,20,30,45 mins, 1,1.25,1.5,2,2.5,3,4,6,8,12,16 h (Days 1,4,7),24 h (Days 2,5,8) ]
      Time to reach maximum observed drug concentration of rhPTH(1-84) administered as a single SC dose of 100 mcg in plasma during a dosing interval between healthy adult volunteer subjects of Japanese descent and matched, non-Hispanic, healthy, adult Caucasian subjects. PK parameters will be calculated from original and baseline-adjusted plasma concentration-time data using noncompartmental methods and all calculations will be based on actual sampling times. Here NHC refers to Non-Hi

      Current Secondary Outcome:

      • Dose Proportionality for Maximum Observed Drug Concentration (Cmax) of rhPTH(1-84) [ Time Frame: 30 and 90 mins predose, 10,20,30,45 mins, 1,1.25,1.5,2,2.5,3,4,6,8,12,16 h (Days 1,4,7),24 h (Days 2,5,8) ]
        Dose proportionality will be assessed for maximum concentration occurring at time of maximum observed concentration of rhPTH(1-84) during a dosing interval when exposed to single SC doses of rhPTH(1-84) at 25 mcg, 50 mcg and 100 mcg in healthy adult volunteer subjects of Japanese descent. Dose proportionality for Cmax will be assessed using the power model.
      • Dose Proportionality for Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of rhPTH(1-84) [ Time Frame: 30 and 90 mins predose, 10,20,30,45 mins, 1,1.25,1.5,2,2.5,3,4,6,8,12,16 h (Days 1,4,7),24 h (Days 2,5,8) ]
        Dose proportionality will be assessed for area under the curve from the time of dosing to the last measurable concentration of rhPTH(1-84) during a dosing interval when exposed to single SC doses of rhPTH(1-84) at 25 mcg, 50 mcg and 100 mcg in healthy adult volunteer subjects of Japanese descent. Dose proportionality for AUClast will be assessed using the power model.
      • Pharmacodynamic (PD) Profile Comparison in Serum Calcium and Phosphate Levels of rhPTH(1-84) [ Time Frame: Non-Hispanic Caucasians: 30 mins predose, 4, 8 and 12 h (Day 1),24 h (Day 2) Japanese Descents: 30 mins predose, 4, 8 and 12 h (Days 1, 4, 7), 24 h (Days 2, 5, 8) ]
        PD profiles in serum calcium and phosphate will be compared in healthy adult volunteer subjects of Japanese descent and matched, non-Hispanic, healthy, adult Caucasian subjects when exposed to 100 mcg SC injection of rhPTH(1-84). Pharmacodynamic parameters will be computed from individual post dose values of serum calcium (uncorrected and corrected for serum albumin levels and both unadjusted and baseline adjusted) and phosphate using non-compartmental methods. PD parameters include AUClast, tmax, Emax and TEmax. PD parameters will be estimated based on both original and baseline-adjusted values of serum calcium and phosphate.
      • Assessment of PD Profiles in Serum Calcium and Phosphate Levels of rhPTH(1-84) [ Time Frame: Non-Hispanic Caucasians: 30 mins predose, 4, 8 and 12 h (Day 1),24 h (Day 2) Japanese Descents: 30 mins predose, 4, 8 and 12 h (Days 1, 4, 7), 24 h (Days 2, 5, 8) ]
        PD profiles in serum calcium and phosphate will be assessed in healthy adult volunteer subjects of Japanese descent when exposed to 25 mcg and 50 mcg SC injection of rhPTH(1-84). Pharmacodynamic parameters will be computed from individual post dose values of serum calcium (uncorrected and corrected for serum albumin levels and both unadjusted and baseline adjusted) and phosphate using non-compartmental methods.
      • Safety and tolerability of rhPTH(1-84) as measured by treatment-emergent adverse events (TEAEs) [ Time Frame: From start of study drug administration to follow-up (up to 40 days) ]
        Safety and tolerability will be determined through assessment of treatment-emergent adverse events (TEAEs), vital signs, electrocardiogram (ECG) findings, and clinical laboratory evaluations for the non-Hispanic, Caucasian subjects and for the subjects of Japanese descent.


      Original Secondary Outcome:

      • Dose Proportionality for Maximum Observed Drug Concentration (Cmax) of rhPTH(1-84) [ Time Frame: 30 and 90 mins predose, 10,20,30,45 mins, 1,1.25,1.5,2,2.5,3,4,6,8,12,16 h (Days 1,4,7),24 h (Days 2,5,8) ]
        Dose proportionality will be assessed for maximum concentration occurring at time of maximum observed concentration of rhPTH(1-84) during a dosing interval when exposed to single SC doses of rhPTH(1-84) at 25 mcg, 50 mcg and 100 mcg in healthy adult volunteer subjects of Japanese descent. Dose proportionality for Cmax will be assessed using the power model.
      • Dose Proportionality for Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of rhPTH(1-84) [ Time Frame: 30 and 90 mins predose, 10,20,30,45 mins, 1,1.25,1.5,2,2.5,3,4,6,8,12,16 h (Days 1,4,7),24 h (Days 2,5,8) ]
        Dose proportionality will be assessed for area under the curve from the time of dosing to the last measurable concentration of rhPTH(1-84) during a dosing interval when exposed to single SC doses of rhPTH(1-84) at 25 mcg, 50 mcg and 100 mcg in healthy adult volunteer subjects of Japanese descent. Dose proportionality for AUClast will be assessed using the power model.
      • Pharmacodynamic (PD) Profile Comparison in Serum Calcium and Phosphate Levels of rhPTH(1-84) [ Time Frame: Non-Hispanic Caucasians: 30 mins predose, 4, 8 and 12 h (Day 1),24 h (Day 2) Japanese Descents: 30 mins predose, 4, 8 and 12 h (Days 1, 4, 7), 24 h (Days 2, 5, 8) ]
        PD profiles in serum calcium and phosphate will be compared in healthy adult volunteer subjects of Japanese descent and matched, non-Hispanic, healthy, adult Caucasian subjects when exposed to 100 mcg SC injection of rhPTH(1-84). Pharmacodynamic parameters will be computed from individual post dose values of serum calcium (uncorrected and corrected for serum albumin levels and both unadjusted and baselineadjusted) and phosphate using non-compartmental methods. PD parameters include AUClast, tmax, Emax and TEmax. PD parameters will be estimated based on both original and baseline-adjusted values of serum calcium and phosphate.
      • Assessment of PD Profiles in Serum Calcium and Phosphate Levels of rhPTH(1-84) [ Time Frame: Non-Hispanic Caucasians: 30 mins predose, 4, 8 and 12 h (Day 1),24 h (Day 2) Japanese Descents: 30 mins predose, 4, 8 and 12 h (Days 1, 4, 7), 24 h (Days 2, 5, 8) ]
        PD profiles in serum calcium and phosphate will be assessed in healthy adult volunteer subjects of Japanese descent when exposed to 25 mcg and 50 mcg SC injection of rhPTH(1-84). Pharmacodynamic parameters will be computed from individual post dose values of serum calcium (uncorrected and corrected for serum albumin levels and both unadjusted and baseline adjusted) and phosphate using non-compartmental methods.
      • Safety and tolerability of rhPTH(1-84) as measured by treatment-emergent adverse events (TEAEs) [ Time Frame: From start of study drug administration to follow-up (up to 40 days) ]
        Safety and tolerability will be determined through assessment of treatment-emergent adverse events (TEAEs), vital signs, electrocardiogram (ECG) findings, and clinical laboratory evaluations for the non-Hispanic, Caucasian subjects and for the subjects of Japanese descent.


      Information By: Shire

      Dates:
      Date Received: May 1, 2017
      Date Started: May 16, 2017
      Date Completion: June 20, 2017
      Last Updated: May 15, 2017
      Last Verified: May 2017