A Phase I Randomized Trial of Once-Daily Versus Twice-Daily Recombinant Human Parathyroid Hormone (1-84) for Hypoparathyroidism.

Ing SW, Finkelman RD, He P, Khan AA, Mannstadt M, Rejnmark L, Song I, Takács I, Wu Y

JBMR plus31 May 2023Cited by 2 (Europe PMC)

PMID37457880PMCIDPMC10339078DOI10.1002/jbm4.10758PepBankPUB-37457880

Summary

Recombinant human parathyroid hormone (1-84), rhPTH(1-84), is an approved adjunctive treatment to oral calcium and active vitamin D for adult patients with hypoparathyroidism; however, there is limited information on the effect of twice daily (BID) dosing of rhPTH(1-84). This was a phase I, open-label, randomized, crossover, multicenter study conducted in adult patients with chronic hypoparathyroidism. The primary objective was to assess the pharmacokinetic profile and pharmacodynamic effects of 1 day of treatment with rhPTH(1-84) administered subcutaneously at 25 μg BID, 50 μg BID, and 100 μg once daily (QD) with or without supplemental oral calcium. Safety and tolerability were evaluated as secondary objectives. In total, 33 patients with chronic hypoparathyroidism completed the study. Treatment with rhPTH(1-84), both BID and QD, over the short-term maintained serum calcium, lowered serum phosphorus, decreased urinary calcium excretion, and increased urinary phosphorus excretion. The decrease in urinary calcium excretion was numerically greater for BID than QD. Generally, baseline-adjusted pharmacokinetic parameters including area under the curve and maximum observed concentration increased with increasing rhPTH(1-84) dose, although this effect was not dose proportional. No new safety findings were observed. Our study revealed no differences thought to be clinically meaningful in pharmacokinetic or pharmacodynamic parameters with BID versus QD rhPTH(1-84) dosing. Future long-term studies are warranted to further elucidate the effects of alternative dosing strategies. © 2023 Takeda Development Center Americas, Inc and The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study10

10 results from studies that gave the peptide. 10 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with chronic hypoparathyroidism, twice-daily rhPTH(1-84) produced a numerically greater urinary calcium reduction than once-daily dosing.
In plain wordsIn adults with chronic hypoparathyroidism, twice-daily rhPTH(1-84) reduced urinary calcium numerically more than once-daily dosing.
Peptide
PTH 1-84 (parathyroid hormone)
Outcome
DecreaseUrinary calcium reduction with twice-daily dosing
Study
n = 33
Comparator
Once-daily rhPTH(1-84)
Analysis
Primary
Outcome group
Kidney function · Kidney and urinary
Studied dose
25 μg twice daily, 50 μg twice daily, or 100 μg once daily · subcutaneous · 1 dayAs given in this study (human).
Source sentences
Summary
The decrease in urinary calcium excretion was numerically greater for BID than QD.
2 context sentences(design, population, supporting numbers)
Summary · context
This was a phase I, open-label, randomized, crossover, multicenter study conducted in adult patients with chronic hypoparathyroidism.
Summary · context
The primary objective was to assess the pharmacokinetic profile and pharmacodynamic effects of 1 day of treatment with rhPTH(1-84) administered subcutaneously at 25 μg BID, 50 μg BID, and 100 μg once daily (QD) with or without supplemental oral calcium.
Show in the study text Report a problemFND-3745788005
02HumanRandomized controlled trialPharmacokinetics
In adults with chronic hypoparathyroidism, baseline-adjusted rhPTH(1-84) area under the curve generally increased with dose, but not proportionally.
In plain wordsIn adults with chronic hypoparathyroidism, rhPTH(1-84) exposure generally increased with dose, but not proportionally.
Peptide
PTH 1-84 (parathyroid hormone)
Outcome
IncreaseArea under the curve dose response
Study
n = 33
Comparator
Lower rhPTH(1-84) doses
Analysis
Primary
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
25 μg twice daily, 50 μg twice daily, or 100 μg once daily · subcutaneous · 1 dayAs given in this study (human).
Source sentences
Summary
Generally, baseline-adjusted pharmacokinetic parameters including area under the curve and maximum observed concentration increased with increasing rhPTH(1-84) dose, although this effect was not dose proportional.
2 context sentences(design, population, supporting numbers)
Summary · context
This was a phase I, open-label, randomized, crossover, multicenter study conducted in adult patients with chronic hypoparathyroidism.
Summary · context
The primary objective was to assess the pharmacokinetic profile and pharmacodynamic effects of 1 day of treatment with rhPTH(1-84) administered subcutaneously at 25 μg BID, 50 μg BID, and 100 μg once daily (QD) with or without supplemental oral calcium.
Show in the study text Report a problemFND-3745788006
03HumanRandomized controlled trialPharmacokinetics
In adults with chronic hypoparathyroidism, baseline-adjusted maximum rhPTH(1-84) concentration generally increased with dose, but not proportionally.
In plain wordsIn adults with chronic hypoparathyroidism, maximum rhPTH(1-84) concentration generally increased with dose, but not proportionally.
Peptide
PTH 1-84 (parathyroid hormone)
Outcome
IncreaseMaximum concentration dose response
Study
n = 33
Comparator
Lower rhPTH(1-84) doses
Analysis
Primary
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
25 μg twice daily, 50 μg twice daily, or 100 μg once daily · subcutaneous · 1 dayAs given in this study (human).
Source sentences
Summary
Generally, baseline-adjusted pharmacokinetic parameters including area under the curve and maximum observed concentration increased with increasing rhPTH(1-84) dose, although this effect was not dose proportional.
2 context sentences(design, population, supporting numbers)
Summary · context
This was a phase I, open-label, randomized, crossover, multicenter study conducted in adult patients with chronic hypoparathyroidism.
Summary · context
The primary objective was to assess the pharmacokinetic profile and pharmacodynamic effects of 1 day of treatment with rhPTH(1-84) administered subcutaneously at 25 μg BID, 50 μg BID, and 100 μg once daily (QD) with or without supplemental oral calcium.
Show in the study text Report a problemFND-3745788007
04HumanRandomized controlled trialPharmacokinetics
In adults with chronic hypoparathyroidism, twice-daily versus once-daily rhPTH(1-84) showed no pharmacokinetic differences considered clinically meaningful.
In plain wordsIn adults with chronic hypoparathyroidism, twice-daily versus once-daily rhPTH(1-84) showed no pharmacokinetic differences considered clinically meaningful.
Peptide
PTH 1-84 (parathyroid hormone)
Outcome
Not applicableClinically meaningful pharmacokinetic differences
Study
n = 33
Comparator
Once-daily rhPTH(1-84)
Analysis
Primary
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
25 μg twice daily, 50 μg twice daily, or 100 μg once daily · subcutaneous · 1 dayAs given in this study (human).
Source sentences
Summary
Our study revealed no differences thought to be clinically meaningful in pharmacokinetic or pharmacodynamic parameters with BID versus QD rhPTH(1-84) dosing.
2 context sentences(design, population, supporting numbers)
Summary · context
This was a phase I, open-label, randomized, crossover, multicenter study conducted in adult patients with chronic hypoparathyroidism.
Summary · context
The primary objective was to assess the pharmacokinetic profile and pharmacodynamic effects of 1 day of treatment with rhPTH(1-84) administered subcutaneously at 25 μg BID, 50 μg BID, and 100 μg once daily (QD) with or without supplemental oral calcium.
Show in the study text Report a problemFND-3745788009
05HumanRandomized controlled trialEfficacy outcome
In adults with chronic hypoparathyroidism, twice-daily versus once-daily rhPTH(1-84) showed no pharmacodynamic differences considered clinically meaningful.
In plain wordsIn adults with chronic hypoparathyroidism, twice-daily versus once-daily rhPTH(1-84) showed no pharmacodynamic differences considered clinically meaningful.
Peptide
PTH 1-84 (parathyroid hormone)
Outcome
Not applicableClinically meaningful pharmacodynamic differences
Study
n = 33
Comparator
Once-daily rhPTH(1-84)
Analysis
Primary
Outcome group
Electrolyte balance · Endocrine and hormones
Studied dose
25 μg twice daily, 50 μg twice daily, or 100 μg once daily · subcutaneous · 1 dayAs given in this study (human).
Source sentences
Summary
Our study revealed no differences thought to be clinically meaningful in pharmacokinetic or pharmacodynamic parameters with BID versus QD rhPTH(1-84) dosing.
2 context sentences(design, population, supporting numbers)
Summary · context
This was a phase I, open-label, randomized, crossover, multicenter study conducted in adult patients with chronic hypoparathyroidism.
Summary · context
The primary objective was to assess the pharmacokinetic profile and pharmacodynamic effects of 1 day of treatment with rhPTH(1-84) administered subcutaneously at 25 μg BID, 50 μg BID, and 100 μg once daily (QD) with or without supplemental oral calcium.
Show in the study text Report a problemFND-3745788010
06HumanNon-randomized trialEfficacy outcome
In adults with chronic hypoparathyroidism, short-term twice- or once-daily rhPTH(1-84) maintained serum calcium.
In plain wordsIn adults with chronic hypoparathyroidism, short-term twice- or once-daily rhPTH(1-84) maintained serum calcium.
Peptide
PTH 1-84 (parathyroid hormone)
Outcome
Not applicableSerum calcium
Study
n = 33
Analysis
Primary
Outcome group
Electrolyte balance · Endocrine and hormones
Studied dose
25 μg twice daily, 50 μg twice daily, or 100 μg once daily · subcutaneous · 1 dayAs given in this study (human).
Source sentences
Summary
Treatment with rhPTH(1-84), both BID and QD, over the short-term maintained serum calcium, lowered serum phosphorus, decreased urinary calcium excretion, and increased urinary phosphorus excretion.
2 context sentences(design, population, supporting numbers)
Summary · context
This was a phase I, open-label, randomized, crossover, multicenter study conducted in adult patients with chronic hypoparathyroidism.
Summary · context
The primary objective was to assess the pharmacokinetic profile and pharmacodynamic effects of 1 day of treatment with rhPTH(1-84) administered subcutaneously at 25 μg BID, 50 μg BID, and 100 μg once daily (QD) with or without supplemental oral calcium.
Show in the study text Report a problemFND-3745788001
07HumanNon-randomized trialEfficacy outcome
In adults with chronic hypoparathyroidism, short-term twice- or once-daily rhPTH(1-84) lowered serum phosphorus.
In plain wordsIn adults with chronic hypoparathyroidism, short-term twice- or once-daily rhPTH(1-84) lowered serum phosphorus.
Peptide
PTH 1-84 (parathyroid hormone)
Outcome
DecreaseSerum phosphorus
Study
n = 33
Analysis
Primary
Outcome group
Electrolyte balance · Endocrine and hormones
Studied dose
25 μg twice daily, 50 μg twice daily, or 100 μg once daily · subcutaneous · 1 dayAs given in this study (human).
Source sentences
Summary
Treatment with rhPTH(1-84), both BID and QD, over the short-term maintained serum calcium, lowered serum phosphorus, decreased urinary calcium excretion, and increased urinary phosphorus excretion.
2 context sentences(design, population, supporting numbers)
Summary · context
This was a phase I, open-label, randomized, crossover, multicenter study conducted in adult patients with chronic hypoparathyroidism.
Summary · context
The primary objective was to assess the pharmacokinetic profile and pharmacodynamic effects of 1 day of treatment with rhPTH(1-84) administered subcutaneously at 25 μg BID, 50 μg BID, and 100 μg once daily (QD) with or without supplemental oral calcium.
Show in the study text Report a problemFND-3745788002
08HumanNon-randomized trialEfficacy outcome
In adults with chronic hypoparathyroidism, short-term twice- or once-daily rhPTH(1-84) decreased urinary calcium excretion.
In plain wordsIn adults with chronic hypoparathyroidism, short-term twice- or once-daily rhPTH(1-84) decreased urinary calcium excretion.
Peptide
PTH 1-84 (parathyroid hormone)
Outcome
DecreaseUrinary calcium excretion
Study
n = 33
Analysis
Primary
Outcome group
Kidney function · Kidney and urinary
Studied dose
25 μg twice daily, 50 μg twice daily, or 100 μg once daily · subcutaneous · 1 dayAs given in this study (human).
Source sentences
Summary
Treatment with rhPTH(1-84), both BID and QD, over the short-term maintained serum calcium, lowered serum phosphorus, decreased urinary calcium excretion, and increased urinary phosphorus excretion.
2 context sentences(design, population, supporting numbers)
Summary · context
This was a phase I, open-label, randomized, crossover, multicenter study conducted in adult patients with chronic hypoparathyroidism.
Summary · context
The primary objective was to assess the pharmacokinetic profile and pharmacodynamic effects of 1 day of treatment with rhPTH(1-84) administered subcutaneously at 25 μg BID, 50 μg BID, and 100 μg once daily (QD) with or without supplemental oral calcium.
Show in the study text Report a problemFND-3745788003
09HumanNon-randomized trialEfficacy outcome
In adults with chronic hypoparathyroidism, short-term twice- or once-daily rhPTH(1-84) increased urinary phosphorus excretion.
In plain wordsIn adults with chronic hypoparathyroidism, short-term twice- or once-daily rhPTH(1-84) increased urinary phosphorus excretion.
Peptide
PTH 1-84 (parathyroid hormone)
Outcome
IncreaseUrinary phosphorus excretion
Study
n = 33
Analysis
Primary
Outcome group
Kidney function · Kidney and urinary
Studied dose
25 μg twice daily, 50 μg twice daily, or 100 μg once daily · subcutaneous · 1 dayAs given in this study (human).
Source sentences
Summary
Treatment with rhPTH(1-84), both BID and QD, over the short-term maintained serum calcium, lowered serum phosphorus, decreased urinary calcium excretion, and increased urinary phosphorus excretion.
2 context sentences(design, population, supporting numbers)
Summary · context
This was a phase I, open-label, randomized, crossover, multicenter study conducted in adult patients with chronic hypoparathyroidism.
Summary · context
The primary objective was to assess the pharmacokinetic profile and pharmacodynamic effects of 1 day of treatment with rhPTH(1-84) administered subcutaneously at 25 μg BID, 50 μg BID, and 100 μg once daily (QD) with or without supplemental oral calcium.
Show in the study text Report a problemFND-3745788004
10HumanNon-randomized trialSafety outcome
In adults with chronic hypoparathyroidism receiving rhPTH(1-84), no new safety findings were observed.
In plain wordsIn adults with chronic hypoparathyroidism receiving rhPTH(1-84), no new safety findings were observed.
Peptide
PTH 1-84 (parathyroid hormone)
Outcome
Not applicableNew safety findings
Study
n = 33
Analysis
Secondary
Outcome group
Adverse events · Whole body
Studied dose
25 μg twice daily, 50 μg twice daily, or 100 μg once daily · subcutaneous · 1 dayAs given in this study (human).
Source sentences
Summary
No new safety findings were observed.
2 context sentences(design, population, supporting numbers)
Summary · context
This was a phase I, open-label, randomized, crossover, multicenter study conducted in adult patients with chronic hypoparathyroidism.
Summary · context
The primary objective was to assess the pharmacokinetic profile and pharmacodynamic effects of 1 day of treatment with rhPTH(1-84) administered subcutaneously at 25 μg BID, 50 μg BID, and 100 μg once daily (QD) with or without supplemental oral calcium.
Show in the study text Report a problemFND-3745788008

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:37 UTC
First added · source update from Europe PMC

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