Clinical Trial: Study to Assess the Blood Concentrations and Actions of Recombinant Human Parathyroid Hormone (rhPTH [1-84]) When Given Once and Twice Daily to Subjects With Hypoparathyroidism

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

Official Title: An Open-Label, Randomized, Crossover Study to Assess the Pharmacokinetic and Pharmacodynamic Profiles of Once Daily and Twice Daily Dose Regimens of Recombinant Human Parathyroid Hormone (rhPTH[1-84])

Brief Summary: This study is being conducted to characterize the effects of twice daily administration of rhPTH(1-84) on the way the body handles rhPTH(1-84) as well as its actions and safety and tolerability over the course of 24 hours as compared with the current once daily dosing regimen of marketed rhPTH(1-84) (marketed in the United States as Natpara®).

Detailed Summary:
Sponsor: Shire

Current Primary Outcome:

  • The pharmacokinetic profile of rhPTH(1-84) as measured by plasma PTH concentrations [ Time Frame: Baseline up to a maximum of 65 days ]
  • The pharmacodynamic effects of rhPTH(1-84) ± supplemental calcium as measured by control of serum calcium [ Time Frame: Baseline up to a maximum of 65 days ]
  • The pharmacodynamic effects of rhPTH(1-84) ± supplemental calcium as measured by urinary calcium excretion [ Time Frame: Baseline up to a maximum of 65 days ]


Original Primary Outcome:

  • Maximum observed concentration maximum (Cmax) of rhPTH(1-84) [ Time Frame: Baseline up to a maximum of 65 days ]
  • Time of maximum concentration (Tmax) of rhPTH(1-84) [ Time Frame: Baseline up to a maximum of 65 days ]
  • Area under the concentration curve (from time zero to the last measurable concentration and from time zero to infinity (AUC0-t and AUC0-inf) of rhPTH(1-84) [ Time Frame: Baseline up to a maximum of 65 days ]
  • Area under the concentration curve from time zero to 24 hours post the first dose (AUC0-24h) of rhPTH(1-84) [ Time Frame: Baseline up to a maximum of 65 days ]
  • Elimination rate constant (Kel) of rhPTH(1-84) [ Time Frame: Baseline up to a maximum of 65 days ]
  • Apparent clearance (CL/F) of rhPTH(1-84) [ Time Frame: Baseline up to a maximum of 65 days ]
  • Apparent volume of distribution (Vz/F) of rhPTH(1-84) [ Time Frame: Baseline up to a maximum of 65 days ]
  • Elimination half-life (t1/2) of rhPTH(1-84) [ Time Frame: Baseline up to a maximum of 65 days ]
  • Area under the concentration curve from time 0 to 24 hours (AUC 0-24h) for serum concentration of calcium [ Time Frame: Baseline up to a maximum of 65 days ]
  • Area under the concentration curve from time 0 to 24 hours (AUC 0-24h) for serum concentration of phosphate [ Time Frame: Baseline up to a maximum of 65 days ]
  • Area under the concentration curve from time 0 to 24 hours (AUC 0-24h) for serum concentr

    Current Secondary Outcome: The safety and tolerability of rhPTH(1-84) as measured by AEs and SAEs [ Time Frame: Baseline to Follow-up (approx. 2 months) ]

    Original Secondary Outcome:

    • Instances of adverse events (AEs) [ Time Frame: Baseline to Follow-up (approx. 2 months) ]
    • Instances of serious adverse events (SAEs) [ Time Frame: Baseline to Follow-up (approx. 2 months) ]
    • Blood safety laboratory values (including hematology, serum chemistries, creatinine clearance) [ Time Frame: Baseline to Follow-up (approx. 2 months) ]
    • Urine safety laboratory values (including urinary chemistries [24-hr urinary calcium, sodium, citrate, phosphate, magnesium, cyclic AMP, and creatinine excretion]) [ Time Frame: Baseline to Follow-up (approx. 2 months) ]
    • Anti-PTH antibody levels [ Time Frame: Baseline up to a maximum of 65 days ]
    • Electrocardiogram (ECG) assessments [ Time Frame: Baseline to Follow-up (approx. 2 months) ]
    • Vital sign assessments [ Time Frame: Baseline to Follow-up (approx. 2 months) ]


    Information By: Shire

    Dates:
    Date Received: April 19, 2016
    Date Started: March 11, 2017
    Date Completion: December 1, 2017
    Last Updated: May 18, 2017
    Last Verified: May 2017