HypoparathyroidismPhase 1PARALLAXNCT02781844

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

A Phase 1 study testing 25mcg rhPTH(1-84), 50mcg rhPTH(1-84) and 100mcg rhPTH(1-84) in people with Hypoparathyroidism, run by Shire at 15 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Hypoparathyroidism
What is being tested?: 25mcg rhPTH(1-84), 50mcg rhPTH(1-84) and 100mcg rhPTH(1-84)
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 34 participants
Where: 15 sitesin 4 countries
Study dates: 3 Apr 2017to 8 Mar 2019
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

An understanding, ability, and willingness to fully comply with study procedures and restrictions.
Ability to voluntarily provide written, signed, and dated informed consent as applicable to participate in the study.
Adult men or women aged greater than or equal (>=) 18 years at the time of consent. The date of participant signature of the informed consent is defined as the beginning of the Screening Period. The Screening Period for this study may encompass both the Administrative Screening Period (if needed) and the Clinical Screening Period. For purposes of this inclusion criterion, age will only be assessed at the time the informed consent is first signed by the study participant.
History of hypoparathyroidism for >=12 months, post-diagnosis, inclusive of historical biochemical evidence of hypocalcemia with concomitant serum intact parathyroid hormone (PTH) concentrations below the lower limit of the laboratory normal range.
Requirement for supplemental oral calcium treatment >=1000 milligrams (mg) elemental calcium per day.
Requirement for therapy with active forms of vitamin D at a minimum dose of >=0.25 microgram (mcg) per day (that is, >=0.25 mcg calcitriol or equivalent per day).

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Serum calcium level within the laboratory normal reference range based on clinical chemistry lab results at the Clinical Screening Visit (based on central and/or local lab results) and Treatment Period 1, Day -2 (based on central and/or local lab results), or if outside of normal range, considered not clinically significant by the investigator.
Urinary calcium excretion >=200mg (5 millimolar [mmol])/24 hour (h), based on a 24-hour collection, collected anytime during the Clinical Screening Period, but prior to check-in to the Clinical Research Center (CRC) at Treatment Period 1, Day -2 (based on central and/or local lab results).
Serum magnesium level within the laboratory normal range at the Clinical Screening Visit or, if outside of normal range, considered not clinically significant by the investigator.
Serum thyroid function tests within normal laboratory limits at the Clinical Screening Visit, or, if outside of normal range, considered as not clinically significant by the investigator.
Serum 25-hydroxyvitamin D (25(OH)D) level between the lower limit of normal and 1.5-fold the laboratory upper limit of normal, or, if outside of this range, considered not clinically significant by the investigator, at the Clinical Screening Visit.
Serum creatinine less than (<) 1.5 mg/ decilitre (dL) (<133 micromole [mmol]/ litre [L]) AND estimated creatinine clearance greater than (>) 60 millilitre (mL)/minute (>1.002mL/ Second [s]) at the Clinical Screening Visit, and serum creatinine <1.5 mg/dL (<133mmol/L) at Treatment Period 1, Day -2.
Male or non-pregnant, non-lactating female who agrees to comply with any applicable contraceptive requirements of the protocol or females of non-childbearing potential.

Who cannot join

Participation in any other investigational drug study in which the last dose of investigational drug occurred within 3 months prior to Day 1 of Treatment Period 1 (or within 5 half-lives, if elimination half-life is greater than 18 days).
Presence or history of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine (with exception of the condition under study), or neurologic system(s) or psychiatric disease as determined by the investigator.
Known history of hypoparathyroidism resulting from an activation mutation in the calcium sensing receptor (CaSR) gene or impaired responsiveness to PTH (pseudohypoparathyroidism).
Any disease that might affect calcium metabolism or calcium-phosphate homeostasis other than hypoparathyroidism, including but not limited to, active hyperthyroidism; poorly controlled insulin-dependent diabetes mellitus or type 2 diabetes mellitus; severe and chronic cardiac, liver or renal disease; Cushing's syndrome; neuromuscular disease such as rheumatoid arthritis; myeloma; pancreatitis; malnutrition; rickets; recent prolonged immobility; active malignancy, bone metastases or a history of skeletal malignancies; primary or secondary hyperparathyroidism; a history of parathyroid carcinoma; hypopituitarism, acromegaly; or multiple endocrine neoplasia types 1 and 2, as determined by the investigator.
5 . In male and female rats, parathyroid hormone caused an increase in the incidence of osteosarcoma (a malignant bone tumor). The occurrence of osteosarcoma was dependent on parathyroid hormone dose and treatment duration. This effect was observed at parathyroid hormone exposure levels ranging from 3 to 71 times the exposure levels in humans receiving a 100 mcg dose of rhPTH(1-84). Therefore, participant who are at increased baseline risk for osteosarcoma such as participant with Paget's disease of bone or unexplained elevations of alkaline phosphatase, pediatric and young adult participants with open epiphyses, participants with hereditary disorders predisposing to osteosarcoma or participant with a prior history of external beam or implant radiation therapy involving the skeleton are excluded.
6. Participants who have a known history of hypercalcemia during initiation of treatment with PTH, PTH analogues or fragments of PTH.

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7. Participants who have a known history of hypocalcemia following abrupt withdrawal of treatment with PTH, PTH analogues or fragments of PTH.
8. Participant dependent on regular parenteral calcium infusions (example, calcium gluconate) to maintain calcium homeostasis within 3 months prior to enrollment, as determined by the investigator.
9. Use of the following medications prior to administration of investigational product within: 14 days- thiazide diuretics; 30 days - loop diuretics, lithium, systemic corticosteroids (medical judgment is required by the investigator. Primarily high doses of systemic corticosteroids [example, prednisone] should be excluded. Stable doses of hydrocortisone [example, as treatment for Addison's disease] may be acceptable); 3 months - calcitonin, cinacalcet hydrochloride, treatment with rhPTH(1-84) or N-terminal PTH or PTH-related peptide fragments or analogs; For females: changes in hormone replacement therapy within 3 months are excluded. Stable (>=3 months) hormone replacement therapy is acceptable; 6 months - fluoride tablets, oral bisphosphonates, methotrexate, growth hormone, digoxin, raloxifene or similar selective estrogen receptor modulators (SERMs); 12 months - intravenous bisphosphonates, drug or alcohol abuse, as determined by the investigator.
10. Presence of any clinically significant results from laboratory tests, vital signs assessments, or electrocardiograms (ECGs), as judged by the investigator.
11. Twelve-lead ECG values (average of triplicate readings) demonstrating QTc>450 millisecond (msec) (males) or >470 msec (females) at the Clinical Screening Visit and/or any time points up to and including predose of Day 1 (Period 1).
12. Any medical condition or prior therapy that, in the opinion of the investigator, would make the participant unsuitable for this study.
13. Positive test result for any of the following viral infections at the Clinical Screening Visit: Hepatitis B surface antigen; hepatitis C; human immunodeficiency virus (HIV) 14. Known significant bleeding diathesis that could preclude multiple venipunctures as determined by the investigator.
15. Participants who have donated a total of 100 mL to 499 mL of whole blood within 30 days prior to dosing, or participants who have donated a total of more than 499 mL of whole blood within 56 days prior to dosing.
16. A positive screen for drugs of abuse at the Clinical Screening Visit, and/or a positive screen for drugs of abuse and alcohol at check-in to the CRC at Treatment Period 1. Participants taking prescription medications that might be detected during the urine screen for drugs of abuse may be enrolled per the investigator's medical judgment.
17. History of a clinically significant illness during the 4 weeks prior to dosing (as determined by the investigator).
18. History of any clinically significant surgery or procedure within the past 8 weeks, as determined by the investigator.
19. History of an allergic response(s) to PTH or PTH analogs, or other clinically significant allergies, as determined by the investigator.

Trial locations and contacts

15 sites in 4 countries.

Country

City, postcode or hospital

15 sites in 4 countries

United States10 sites

Massachusetts General Hospital
Boston, Massachusetts, 02114
Ohio State University Wexner Medical Center
Columbus, Ohio, 43201
Indiana University
Indianapolis, Indiana, 46202
New Orleans Center for Clinical Research (NOCCR) - Knoxville
Knoxville, Tennessee, 37920
University Of Kentucky School of Medicine
Lexington, Kentucky, 40536-0298
Crescent City Clinical Research Center, LLC
Metairie, Louisiana, 70006
Columbia University Medical Center
New York, New York, 10032
Providence Clinical Research
North Hollywood, California, 91606
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Mayo Clinic - PPDS
Rochester, Minnesota, 55905

Other trials in United States

Hungary3 sites

Semmelweis Egyetem
Budapest, 1083
Pécsi Tudományegyetem
Pécs, 7624
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
Szeged, Csongrád megye, 6720

Other trials in Hungary

Canada1 site

CHU de Quebec-Universite Laval
Québec, G1V 4G2

Other trials in Canada

Denmark1 site

Aarhus Universitetshospital
Aarhus N, Central Jutland, 8200

Other trials in Denmark

About this study

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]) Administered Subcutaneously to Subjects With Hypoparathyroidism

Conditions: Hypoparathyroidism
Being tested: 25mcg rhPTH(1-84), 50mcg rhPTH(1-84), 100mcg rhPTH(1-84)
Medical subject headings: Hypoparathyroidism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

25mcg rhPTH(1-84)Drug
Also called PTH
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.
50mcg rhPTH(1-84)Drug
Also called PTH
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
100mcg rhPTH(1-84)Drug
Also called PTH
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.

Study groups in NCT02781844
Study group	Role	What they receive
A/B or B/A	Experimental	Participants will be randomized to either receive 25 microgram (mcg) rhPTH(1-84) twice daily with no calcium for treatment period 1 and 100mcg rhPTH(1-84) once daily with no calcium for treatment period 2; or 100mcg rhPTH(1-84) once daily with no calcium for treatment period 1 and 25mcg rhPTH(1-84) BID with no calcium for treatment period 2 Receives: Drug: 25mcg rhPTH(1-84); Drug: 100mcg rhPTH(1-84)
C/B or B/C	Experimental	Participants will be randomized to either receive 50mcg rhPTH(1-84) twice daily with no calcium for treatment period 1 and 100mcg rhPTH(1-84) once daily with no calcium for treatment period 2; or 100mcg rhPTH(1-84) once daily with no calcium for treatment period 1 and 50mcg rhPTH(1-84) twice daily with no calcium for treatment period 2 Receives: Drug: 50mcg rhPTH(1-84); Drug: 100mcg rhPTH(1-84)
D/E or E/D	Experimental	Participants will be randomized to either receive 25mcg rhPTH(1-84) twice daily with calcium for treatment period 1 and 100mcg rhPTH(1-84) once daily with calcium for treatment period 2; or 100mcg rhPTH(1-84) once daily with calcium for treatment period 1 and 25mcg rhPTH(1-84) twice daily with calcium for treatment period 2 Receives: Drug: 25mcg rhPTH(1-84); Drug: 100mcg rhPTH(1-84)
F/E or E/F	Experimental	Participants will be randomized to either receive 50mcg rhPTH(1-84) twice daily with calcium for treatment period 1 and 100mcg rhPTH(1-84) once daily with calcium for treatment period 2; or 100mcg rhPTH(1-84) once daily with calcium for treatment period 1 and 50mcg rhPTH(1-84) twice daily with calcium for treatment period 2 Receives: Drug: 50mcg rhPTH(1-84); Drug: 100mcg rhPTH(1-84)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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 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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 1- QD: Pre-dose up to 24 hours post dose, Day 2- BID: Pre-dose up to 24 hours post dose

Secondary outcomes (1)

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.
Measured: From signing of informed consent up to follow up (up to Day 182)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

3 Apr 20178 Mar 2019

First posted25 May 2016 (estimated)
Study start3 Apr 2017
Primary completion8 Mar 2019
Study completion8 Mar 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HypoparathyroidismStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 34 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02781844
Sponsor's protocol ID: SHP634-101
Other IDs: 2015-004757-40, 2015
Acronym: PARALLAX
Status last verified: May 2021
First submitted: 19 Apr 2016
Last updated: 25 May 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 25 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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]) Administered Subcutaneously to Subjects With Hypoparathyroidism
ClinicalTrials.gov ID: NCT02781844
Acronym / sponsor ID: PARALLAX / SHP634-101
Conditions: Hypoparathyroidism
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 34 participants (actual)
Lead sponsor: ShireIndustry (pharma, biotech, devices)
Study start: 3 Apr 2017 (actual)
Primary completion: 8 Mar 2019 (actual)
Study completion: 8 Mar 2019 (actual)
First posted: 25 May 2016 (estimated)
Results: Posted 9 Apr 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
A/B or B/A	Experimental	Drug: 25mcg rhPTH(1-84), Drug: 100mcg rhPTH(1-84)Participants will be randomized to either receive 25 microgram (mcg) rhPTH(1-84) twice daily with no calcium for treatment period 1 and 100mcg rhPTH(1-84) once daily with no calcium for treatment period 2; or 100mcg rhPTH(1-84) once daily with no calcium for treatment period 1 and 25mcg rhPTH(1-84) BID with no calcium for treatment period 2
C/B or B/C	Experimental	Drug: 50mcg rhPTH(1-84), Drug: 100mcg rhPTH(1-84)Participants will be randomized to either receive 50mcg rhPTH(1-84) twice daily with no calcium for treatment period 1 and 100mcg rhPTH(1-84) once daily with no calcium for treatment period 2; or 100mcg rhPTH(1-84) once daily with no calcium for treatment period 1 and 50mcg rhPTH(1-84) twice daily with no calcium for treatment period 2
D/E or E/D	Experimental	Drug: 25mcg rhPTH(1-84), Drug: 100mcg rhPTH(1-84)Participants will be randomized to either receive 25mcg rhPTH(1-84) twice daily with calcium for treatment period 1 and 100mcg rhPTH(1-84) once daily with calcium for treatment period 2; or 100mcg rhPTH(1-84) once daily with calcium for treatment period 1 and 25mcg rhPTH(1-84) twice daily with calcium for treatment period 2
F/E or E/F	Experimental	Drug: 50mcg rhPTH(1-84), Drug: 100mcg rhPTH(1-84)Participants will be randomized to either receive 50mcg rhPTH(1-84) twice daily with calcium for treatment period 1 and 100mcg rhPTH(1-84) once daily with calcium for treatment period 2; or 100mcg rhPTH(1-84) once daily with calcium for treatment period 1 and 50mcg rhPTH(1-84) twice daily with calcium for treatment period 2

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

An understanding, ability, and willingness to fully comply with study procedures and restrictions.
Ability to voluntarily provide written, signed, and dated informed consent as applicable to participate in the study.
Adult men or women aged greater than or equal (>=) 18 years at the time of consent. The date of participant signature of the informed consent is defined as the beginning of the Screening Period. The Screening Period for this study may encompass both the Administrative Screening Period (if needed) and the Clinical Screening Period. For purposes of this inclusion criterion, age will only be assessed at the time the informed consent is first signed by the study participant.
History of hypoparathyroidism for >=12 months, post-diagnosis, inclusive of historical biochemical evidence of hypocalcemia with concomitant serum intact parathyroid hormone (PTH) concentrations below the lower limit of the laboratory normal range.
Requirement for supplemental oral calcium treatment >=1000 milligrams (mg) elemental calcium per day.

Key exclusion criteria (18 listed)

Participation in any other investigational drug study in which the last dose of investigational drug occurred within 3 months prior to Day 1 of Treatment Period 1 (or within 5 half-lives, if elimination half-life is greater than 18 days).
Presence or history of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine (with exception of the condition under study), or neurologic system(s) or psychiatric disease as determined by the investigator.
Known history of hypoparathyroidism resulting from an activation mutation in the calcium sensing receptor (CaSR) gene or impaired responsiveness to PTH (pseudohypoparathyroidism).
Any disease that might affect calcium metabolism or calcium-phosphate homeostasis other than hypoparathyroidism, including but not limited to, active hyperthyroidism; poorly controlled insulin-dependent diabetes mellitus or type 2 diabetes mellitus; severe and chronic cardiac, liver or renal disease; Cushing's syndrome; neuromuscular disease such as rheumatoid arthritis; myeloma; pancreatitis; malnutrition; rickets; recent prolonged immobility; active malignancy, bone metastases or a history of skeletal malignancies; primary or secondary hyperparathyroidism; a history of parathyroid carcinoma; hypopituitarism, acromegaly; or multiple endocrine neoplasia types 1 and 2, as determined by the investigator.
5 . In male and female rats, parathyroid hormone caused an increase in the incidence of osteosarcoma (a malignant bone tumor). The occurrence of osteosarcoma was dependent on parathyroid hormone dose and treatment duration. This effect was observed at parathyroid hormone exposure levels ranging from 3 to 71 times the exposure levels in humans receiving a 100 mcg dose of rhPTH(1-84). Therefore, participant who are at increased baseline risk for osteosarcoma such as participant with Paget's disease of bone or unexplained elevations of alkaline phosphatase, pediatric and young adult participants with open epiphyses, participants with hereditary disorders predisposing to osteosarcoma or participant with a prior history of external beam or implant radiation therapy involving the skeleton are excluded.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
25mcg rhPTH(1-84)Also: PTHParticipants 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.	Drug	A/B or B/A, D/E or E/D
50mcg rhPTH(1-84)Also: PTHParticipants 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	Drug	C/B or B/C, F/E or E/F
100mcg rhPTH(1-84)Also: PTHParticipants 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.	Drug	A/B or B/A, C/B or B/C, D/E or E/D, F/E or E/F

Primary outcome

Time of Maximum Observed Concentration (Cmax) During a Dosing Interval (Tmax) of Baseline Adjusted rhPTH(1-84)
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
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.
Maximum Plasma Concentration (Cmax) of Baseline Adjusted rhPTH(1-84)
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
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.
Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Baseline Adjusted rhPTH(1-84)
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
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.
Area Under the Curve Extrapolated to Infinity (AUCinf) of Baseline Adjusted rhPTH(1-84)
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
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.
Area Under the Concentration Curve From Time Zero to 24 Hours Post the First Dose (AUC0-24) of Baseline Adjusted rhPTH(1-84)
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
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.
Area Under the Concentration Curve From Time Zero to 12 Hours Post the First Dose (AUC0-12) of Baseline Adjusted rhPTH(1-84)
Time frame: BID: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12 hours post-dose
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).
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)
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
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).
Terminal Half-Life (t1/2) of Baseline Adjusted rhPTH(1-84)
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
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.
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
Time frame: 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.
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
Time frame: 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 to Maximum Effect (TEmax) of Baseline-Adjusted Serum Calcium Concentrations on Day -1
Time frame: 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.
Maximum Effect (Emax) of Baseline-Adjusted Serum Calcium Concentrations on Day -1
Time frame: 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.
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
Time frame: Day1- QD: Pre-dose up to 24 hours post dose, Day2- BID: Pre-dose up to 36 hours post dose
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.
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
Time frame: Day1- QD: Pre-dose up to 24 hours post dose, Day2- BID: Pre-dose up to 36 hours post dose
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 to Maximum Effect (TEmax) of Baseline-Adjusted Serum Calcium Concentrations on Day 1/Day 2
Time frame: Day1- QD: Pre-dose up to 24 hours post dose, Day2- BID: Pre-dose up to 36 hours post dose
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.
Maximum Effect (Emax) of Baseline-Adjusted Serum Calcium Concentrations on Day 1/Day 2
Time frame: Day1- QD: Pre-dose up to 24 hours post dose, Day2- BID: Pre-dose up to 36 hours post dose
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.
Total Amount of Urinary Calcium Excretion to Total Relative Amount of Creatinine Over 24 Hours by Day -1
Time frame: Day -1
Total amount of urinary calcium excretion to total relative amount of creatinine over 24 hours by Day -1 was reported.
Total Amount of Urinary Calcium Excretion to Total Relative Amount of Creatinine Over 24 Hours by Day 1/ Day 2
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 amount of urinary calcium excretion to total relative amount of creatinine over 24 hours by Day 1/ Day 2 was reported.
Total Urinary Excretion of Calcium Over 24 Hours by Day -1
Time frame: Day -1
Total urinary excretion of calcium over 24 Hours by Day -1 was reported.
Total Urinary Excretion of Calcium Over 24 Hours by Day 1/ Day 2
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 Day1/Day 2 was reported.

1 secondary outcome

Number of Participants With Treatment Emergent Adverse Events (TEAE's)
Time frame: From signing of informed consent up to follow up (up to Day 182)

Results and safety

Results posted to the registry on 9 Apr 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort I: Treatment A / B	5	5
Cohort I: Treatment B / A	4	4
Cohort II: Treatment C / B	4	4
Cohort II: Treatment B / C	4	4
Cohort III: Treatment D / E	4	4
Cohort III: Treatment E / D	5	4
Cohort IV: Treatment F / E	4	4
Cohort IV: Treatment E / F	4	4

Primary outcome: Time of Maximum Observed Concentration (Cmax) During a Dosing Interval (Tmax) of Baseline Adjusted rhPTH(1-84)

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. Median (Full Range). Unit: hours

Measure	Cohort I: Treatment A n = 8	Cohort II: Treatment C n = 8	Cohort I+II: Treatment B n = 15	Cohort III: Treatment D n = 8	Cohort IV: Treatment F n = 6	Cohort III + IV: Treatment E n = 14
Value	7.108 (0.18 to 14.07)	7.083 (0.17 to 13.50)	0.333 (0.17 to 4.17)	1.000 (0.15 to 14.00)	12.167 (0.17 to 13.50)	0.667 (0.12 to 4.00)

Population analysed: Pharmacokinetic (PK) analysis set consisted of all enrolled participants who did not have major protocol violations that affected the validity of the PK results, received at least 1 dose of rhPTH(1-84) and had at least 1 evaluable postdose PK concentration value available for 1 dose regimen.

Primary outcome: Maximum Plasma Concentration (Cmax) of Baseline Adjusted rhPTH(1-84)

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. Geometric mean (Geometric Coefficient of Variation). Unit: picogram per milliliter (pg/mL)

Measure	Cohort I: Treatment A n = 8	Cohort II: Treatment C n = 8	Cohort I+II: Treatment B n = 15	Cohort III: Treatment D n = 8	Cohort IV: Treatment F n = 6	Cohort III + IV: Treatment E n = 14
Value	136.9 (50.9)	213.6 (51.6)	339.1 (137.8)	120.9 (83.6)	100.5 (106.2)	240.8 (69.6)

Population analysed: PK analysis set. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.

Primary outcome: Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Baseline Adjusted rhPTH(1-84)

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. Geometric mean (Geometric Coefficient of Variation). Unit: hour*picogram per milliliter (h*pg/mL)

Measure	Cohort I: Treatment A n = 8	Cohort II: Treatment C n = 8	Cohort I+II: Treatment B n = 15	Cohort III: Treatment D n = 8	Cohort IV: Treatment F n = 6	Cohort III + IV: Treatment E n = 13
Value	496.0 (34.1)	653.2 (25.5)	901.1 (448.5)	205.0 (106.6)	261.1 (77.6)	1044.9 (58.0)

Population analysed: PK analysis set. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure and at specific category.

Primary outcome: Area Under the Curve Extrapolated to Infinity (AUCinf) of Baseline Adjusted rhPTH(1-84)

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. Geometric mean (Geometric Coefficient of Variation). Unit: h*pg/mL

Measure	Cohort I: Treatment A n = 4	Cohort II: Treatment C n = 7	Cohort I+II: Treatment B n = 13	Cohort III: Treatment D n = 3	Cohort IV: Treatment F n = 1	Cohort III + IV: Treatment E n = 12
Value	484.8 (48.4)	677.7 (22.9)	1567.6 (36.7)	255.0 (198.3)	600.8 (NA)	1043.5 (50.4)

Population analysed: PK analysis set. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure and at specific category.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: From signing of informed consent up to follow up (up to Day 182). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort I: Treatment A	0 of 9 (0%)	3 of 9 (33.3%)	0 of 9
Cohort II: Treatment C	0 of 8 (0%)	1 of 8 (12.5%)	0 of 8
Cohort I+II: Treatment B	0 of 17 (0%)	4 of 17 (23.5%)	0 of 17
Cohort III: Treatment D	0 of 8 (0%)	5 of 8 (62.5%)	0 of 8
Cohort IV: Treatment F	0 of 8 (0%)	3 of 8 (37.5%)	0 of 8
Cohort III + IV: Treatment E	0 of 17 (0%)	7 of 17 (41.2%)	0 of 17

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Study Director study director

Takeda

15 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 25mcg rhPTH(1-84), 50mcg rhPTH(1-84) and 100mcg rhPTH(1-84) in people with Hypoparathyroidism, run by Shire at 15 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, Hungary, Canada, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time of Maximum Observed Concentration (Cmax) During a Dosing Interval (Tmax) of Baseline Adjusted rhPTH(1-84) (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). The study lists 20 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02781844.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2021.