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® and in the EU as Natpar).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
34
Participants will receive rhPTH(1-84) as twice-daily regimen (12 hours apart) of two 25mcg doses without calcium in cohort 1 and with calcium in cohort 3.
Participants will receive rhPTH(1-84) as twice daily regimen (12 hours apart) of two 50mcg doses without calcium in cohort 2 and with calcium in cohort 4
Participants will receive rhPTH(1-84) as once-daily regimen of one 100 mcg dose without calcium in cohort 1 and 2 and with calcium in cohort 3 and 4 in the morning.
Providence Clinical Research
North Hollywood, California, United States
Indiana University
Indianapolis, Indiana, United States
Time of Maximum Observed Concentration (Cmax) During a Dosing Interval (Tmax) of Baseline Adjusted rhPTH(1-84)
Baseline-adjusted rhPTH(1-84) concentrations (participant- and period-specific) were calculated by subtracting baseline endogenous PTH from the raw PTH concentrations. The baseline was defined as premorning-dose endogenous rhPTH(1-84) level on Day 1 for each treatment period. Tmax of baseline adjusted rhPTH(1-84) was reported. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Time frame: QD: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12,16 and 24 hours post-dose ; BID: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12 hours,12 hour 10 minutes,12 hour 20 minutes,12 hour 30 minutes,13 hours, 13 hour 30 minutes,14,16,20,22,24,28 and 36 hours post-dose
Maximum Plasma Concentration (Cmax) of Baseline Adjusted rhPTH(1-84)
Baseline-adjusted rhPTH(1-84) concentrations (participant- and period-specific) were calculated by subtracting baseline endogenous PTH from the raw PTH concentrations. The baseline was defined as premorning-dose endogenous rhPTH(1-84) level on Day 1 for each treatment period. Cmax of baseline adjusted rhPTH(1-84) was reported.
Time frame: QD: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12,16 and 24 hours post-dose; BID: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12 hours,12 hour 10 minutes,12 hour 20 minutes,12 hour 30 minutes,13 hours, 13 hour 30 minutes,14,16,20,22,24,28 and 36 hours post-dose
Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Baseline Adjusted rhPTH(1-84)
Baseline-adjusted rhPTH(1-84) concentrations (participant- and period-specific) were calculated by subtracting baseline endogenous PTH from the raw PTH concentrations. The baseline was defined as premorning-dose endogenous rhPTH(1-84) level on Day 1 for each treatment period. AUClast of baseline adjsuted plasma rhPTH(1-84) was reported.
Time frame: QD: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12,16 and 24 hours post-dose; BID: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12 hours,12 hour 10 minutes,12 hour 20 minutes,12 hour 30 minutes,13 hours, 13 hour 30 minutes,14,16,20,22,24,28 and 36 hours post-dose
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University Of Kentucky School of Medicine
Lexington, Kentucky, United States
Crescent City Clinical Research Center, LLC
Metairie, Louisiana, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Mayo Clinic - PPDS
Rochester, Minnesota, United States
Columbia University Medical Center
New York, New York, United States
Ohio State University Wexner Medical Center
Columbus, Ohio, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
New Orleans Center for Clinical Research (NOCCR) - Knoxville
Knoxville, Tennessee, United States
...and 5 more locations
Area Under the Curve Extrapolated to Infinity (AUCinf) of Baseline Adjusted rhPTH(1-84)
Baseline-adjusted rhPTH(1-84) concentrations (participant- and period-specific) were calculated by subtracting baseline endogenous PTH from the raw PTH concentrations. The baseline was defined as premorning-dose endogenous rhPTH(1-84) level on Day 1 for each treatment period. AUCinf of baseline adjusted rhPTH(1-84) was reported.
Time frame: QD: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12,16 and 24 hours post-dose; BID: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12 hours,12 hour 10 minutes,12 hour 20 minutes,12 hour 30 minutes,13 hours, 13 hour 30 minutes,14,16,20,22,24,28 and 36 hours post-dose
Area Under the Concentration Curve From Time Zero to 24 Hours Post the First Dose (AUC0-24) of Baseline Adjusted rhPTH(1-84)
Baseline-adjusted rhPTH(1-84) concentrations (participant- and period-specific) were calculated by subtracting baseline endogenous PTH from the raw PTH concentrations. The baseline was defined as premorning-dose endogenous rhPTH(1-84) level on Day 1 for each treatment period. AUC0-24 of baseline adjusted rhPTH(1-84) was reported.
Time frame: QD: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12,16 and 24 hours post-dose; BID: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12 hours,12 hour 10 minutes,12 hour 20 minutes,12 hour 30 minutes,13 hours, 13 hour 30 minutes,14,16,20,22,24 hours post-dose
Area Under the Concentration Curve From Time Zero to 12 Hours Post the First Dose (AUC0-12) of Baseline Adjusted rhPTH(1-84)
Baseline-adjusted rhPTH(1-84) concentrations (participant- and period-specific) were calculated by subtracting baseline endogenous PTH from the raw PTH concentrations. The baseline was defined as premorning-dose endogenous rhPTH(1-84) level on Day 1 for each treatment period. AUC0-12 of baseline adjusted rhPTH(1-84) was reported. AUC(0-12) was planned, analyzed and reported only in participants who received BID treatment ( Treatment A, Treatment C, Treatment D, Treatment F).
Time frame: BID: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12 hours post-dose
Area Under the Concentration Curve From Time of the Second Dose to 12 Hours Post the Second Dose (AUC12-24) of Baseline Adjusted rhPTH(1-84)
Baseline-adjusted rhPTH(1-84) concentrations (participant- and period-specific) were calculated by subtracting baseline endogenous PTH from the raw PTH concentrations. The baseline was defined as premorning-dose endogenous rhPTH(1-84) level on Day 1 for each treatment period. AUC12-24 of baseline adjusted rhPTH(1-84) was reported. AUC(12-24) was planned, analyzed and reported only in participants who received BID treatment ( Treatment A, Treatment C, Treatment D, Treatment F).
Time frame: BID: 12 hours,12 hour 10 minutes,12 hour 20 minutes,12 hour 30 minutes,13 hours, 13 hour 30 minutes,14,16,20,22,24 hours post-dose
Terminal Half-Life (t1/2) of Baseline Adjusted rhPTH(1-84)
Baseline-adjusted rhPTH(1-84) concentrations (participant- and period-specific) were calculated by subtracting baseline endogenous PTH from the raw PTH concentrations. The baseline was defined as premorning-dose endogenous rhPTH(1-84) level on Day 1 for each treatment period. T1/2 of baseline adjusted rhPTH(1-84) was reported.
Time frame: QD: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12,16 and 24 hours post-dose; BID: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12 hours,12 hour 10 minutes,12 hour 20 minutes,12 hour 30 minutes,13 hours, 13 hour 30 minutes,14,16,20,22,24,28 and 36 hours post-dose
Area Under the Concentration-Time Curve That is Above the Baseline, From Time 0 to 24 Hours (AUCabove) of Baseline-Adjusted Serum Calcium Concentrations on Day -1
Baseline-adjusted concentrations calculated by subtracting the appropriate baseline values from the raw concentrations at each time point. AUCabove of baseline-adjusted serum calcium (albumin-corrected) and total calcium (calcium \[uncorrected\]) concentrations on Day -1 was reported. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Time frame: Day -1
Area Under the Concentration-Time Curve That is Below the Baseline, From Time 0 to 24 Hours (AUCbelow) of Baseline-Adjusted Serum Calcium Concentrations on Day -1
Baseline-adjusted concentrations calculated by subtracting the appropriate baseline values from the raw concentrations at each time point. AUCbelow of baseline-adjusted serum calcium (albumin-corrected) and total calcium (calcium \[uncorrected\]) concentrations on Day -1 was reported.
Time frame: Day -1
Time to Maximum Effect (TEmax) of Baseline-Adjusted Serum Calcium Concentrations on Day -1
Baseline-adjusted concentrations calculated by subtracting the appropriate baseline values from the raw concentrations at each time point. TEmax of baseline-adjusted serum calcium (albumin-corrected) and total calcium (calcium \[uncorrected\]) concentrations on Day -1 were reported.
Time frame: Day -1
Maximum Effect (Emax) of Baseline-Adjusted Serum Calcium Concentrations on Day -1
Baseline-adjusted concentrations calculated by subtracting the appropriate baseline values from the raw concentrations at each time point. Emax of baseline-adjusted serum calcium (albumin-corrected) and total calcium (calcium \[uncorrected\]) concentrations on Day -1 were reported.
Time frame: Day -1
Area Under the Concentration-Time Curve That is Above the Baseline, From Time 0 to 24 Hours (AUCabove) of Baseline-Adjusted Serum Calcium Concentrations on Day 1/Day 2
Baseline-adjusted concentrations calculated by subtracting the appropriate baseline values from the raw concentrations at each time point. AUCabove of baseline-adjusted serum calcium (albumin-corrected) and total calcium (calcium \[uncorrected\]) concentrations on Day 1/Day 2 were reported.
Time frame: Day1- QD: Pre-dose up to 24 hours post dose, Day2- BID: Pre-dose up to 36 hours post dose
Area Under the Concentration-Time Curve That is Below the Baseline, From Time 0 to 24 Hours (AUCbelow) of Baseline-Adjusted Serum Calcium Concentrations on Day 1/Day 2
Baseline-adjusted concentrations calculated by subtracting the appropriate baseline values from the raw concentrations at each time point. AUCbelow of baseline-adjusted serum calcium (albumin-corrected) and total calcium (calcium \[uncorrected\]) concentrations on Day 1/Day 2 was reported.
Time frame: Day1- QD: Pre-dose up to 24 hours post dose, Day2- BID: Pre-dose up to 36 hours post dose
Time to Maximum Effect (TEmax) of Baseline-Adjusted Serum Calcium Concentrations on Day 1/Day 2
Baseline-adjusted concentrations calculated by subtracting the appropriate baseline values from the raw concentrations at each time point. TEmax of baseline-adjusted serum calcium (albumin-corrected) and total calcium (calcium \[uncorrected\]) concentrations on Day 1/Day 2 were reported.
Time frame: Day1- QD: Pre-dose up to 24 hours post dose, Day2- BID: Pre-dose up to 36 hours post dose
Maximum Effect (Emax) of Baseline-Adjusted Serum Calcium Concentrations on Day 1/Day 2
Baseline-adjusted concentrations calculated by subtracting the appropriate baseline values from the raw concentrations at each time point. Emax of baseline-adjusted serum calcium (albumin-corrected) and total calcium (calcium \[uncorrected\]) concentrations on Day 1/Day 2 were reported.
Time frame: Day1- QD: Pre-dose up to 24 hours post dose, Day2- BID: Pre-dose up to 36 hours post dose
Total Amount of Urinary Calcium Excretion to Total Relative Amount of Creatinine Over 24 Hours by Day -1
Total amount of urinary calcium excretion to total relative amount of creatinine over 24 hours by Day -1 was reported.
Time frame: Day -1
Total Amount of Urinary Calcium Excretion to Total Relative Amount of Creatinine Over 24 Hours by Day 1/ Day 2
Total amount of urinary calcium excretion to total relative amount of creatinine over 24 hours by Day 1/ Day 2 was reported.
Time frame: Day 1- QD: Pre-dose up to 24 hours post dose, Day 2- BID: Pre-dose up to 24 hours post dose
Total Urinary Excretion of Calcium Over 24 Hours by Day -1
Total urinary excretion of calcium over 24 Hours by Day -1 was reported.
Time frame: Day -1
Total Urinary Excretion of Calcium Over 24 Hours by Day 1/ Day 2
Total urinary excretion of calcium over 24 hours by Day1/Day 2 was reported.
Time frame: Day 1- QD: Pre-dose up to 24 hours post dose, Day 2- BID: Pre-dose up to 24 hours post dose
Number of Participants With Treatment Emergent Adverse Events (TEAE's)
An AE that occured during the study was considered a TEAE if it had a start date/time on or after the first dose of investigational product or if it had a start date before the date of the first dose of investigational product, but increased in severity on or after the date/time of the first dose of investigational product. Number of participants with TEAE's were reported.
Time frame: From signing of informed consent up to follow up (up to Day 182)