An Open-Label, Randosized, 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]) Administered Subcutaneously to Subjects with Hypoparathyroidism (SHP634-101)

Study identification

• PURI:
  https://redirect.ema.europa.eu/resource/46482
• EU PAS number:
  EUPAS13269
• Study ID:
  46482
• Official title and acronym:
  An Open-Label, Randosized, 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]) Administered Subcutaneously to Subjects with Hypoparathyroidism (SHP634-101)
• DARWIN EU® study:
  No
• Study countries:
  Canada

  United States
• Study description:
  Prior to 2015, in the absence of an approved PTH replacement therapy, management of hypoparathyroidism consisted of supplemental oral calcium and active vitamin D in pharmacological doses sufficient to maintain the serum calcium level without the disabling symptoms of hypocalcemia. Additional calcium load that results from supplementation with exogenous calcium and active vitamin D contributes to the hypercalciuria and renal risks often noted in patients with hyperparathyroidism. In an effort to limit the extent and effect of hypercalciuria, thiazide diuretics can be helpful since they promote renal calcium reabsorption. However, thiazides are associated with their own adverse events including hypokalemia and, more importantly, have no proven long-term effect to reduce hypercalciuria or kidney damage or established safety profile. The investigational product (rhPTH1-84) is a recombinant human PTH that is identical in structure to endogenous human PTH, a single-chain polypeptide consisting of 84 amino acid residues and is manufactured using a strain of Escherichia coli modified by recombinant DNA technology. rhPTH(1-84) was approved for marketing in the United States on 23 January 2015 under the brand name Natpara® as a once-daily injectable dose as an adjunct to calcium and vitamin D to control hypocalcemia in patients with hypoparathyroidism. The present study is being conducted to characterize the effects of twice-daily administration of rhPTH(1-84) on pharmacokinetics, pharmacodynamics, safety and tolerability over the course of 24 hours as compared with the current once-daily dosing regimen.
• Study status:
  Finalised

Research institutions and networks

Institutions

Shire

Study timelines

Date when funding contract was signed

Planned: 26/04/2015

Actual: 01/03/2016

Study start date

Planned: 01/04/2015

Actual: 04/03/2017

Date of final study report

Planned: 01/04/2018

Actual: 20/02/2020

Sources of funding

Pharmaceutical company and other private sector 

More details on funding

Shire

Study protocol

Initial protocol

SHP634-101_Protocol Amendment 5_redacted_A

Regulatory

• Was the study required by a regulatory body?:
  No
• Is the study required by a Risk Management Plan (RMP)?:
  Not applicable