HypoparathyroidismPhase 1NCT03150108

Study of rhPTH(1-84) in Japanese Healthy Subjects Compared With Matched Caucasian Healthy Adult Subjects

A Phase 1 study testing rhPTH(1-84) in people with Hypoparathyroidism, run by Shire at 1 site in United States.

Completed

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

Trial summary

The purpose of this study is to compare how rhPTH(1-84) affects the body between healthy adults of Japanese descent and matched, healthy Caucasian adults. Read more about this study

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Hypoparathyroidism
What is being tested?: rhPTH(1-84)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 1 siteUnited States
Study dates: 16 May 2017to 26 Jun 2017
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 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Ability to voluntarily provide written, signed, and dated informed consent as applicable to participate in the study.
An understanding, ability, and willingness to fully comply with study procedures and restrictions.
Age 18-65 inclusive at the time of consent. The date of signature of the informed consent is defined as the beginning of the screening period. This inclusion criterion will only be assessed at the first screening visit.
Subjects must be either:
A subject of Japanese descent born in Japan, who has resided outside of Japan for no longer than 5 years and is of Japanese parentage, defined as having 2 Japanese parents, and 4 Japanese grandparents, all born in Japan.
A non-hispanic, Caucasian subject who has 2 non-hispanic, Caucasian parents and 4 non-hispanic, Caucasian grandparents.

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Male or nonpregnant, nonlactating female who agrees to comply with any applicable contraceptive requirements of the protocol or females of nonchildbearing potential.
Considered "healthy" by the investigator. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead electrocardiogram (ECG), hematology, blood chemistry, and urinalysis.
Body mass index between 18.5 and 28 kilogram per square meter (kg/m^2), inclusive, with a body weight greater than or equal to (>=) 45 kg (99 pounds [lbs]). This inclusion criterion will only be assessed at the first screening visit.
Willing and able to consume standardized meals during the confinement period of the study. All subjects will be required to consume the identical meals on study days when serial pharmacokinetic (PK) and pharmacodynamic (PD) blood samples are collected.
A clinical safety laboratory parameter of hemoglobin greater than (>) 11.7 gram per deciliter (g/dl) (females) or 13.1 g/dl (males) and less than (<) 16 g/dl (females) or 17.4 g/dl (males) or, if out of this range, deemed not clinically significant by the principal investigator.
Total serum calcium within laboratory normal limits.
Serum parathyroid hormone (PTH) levels within laboratory normal limits.

Who cannot join

History of any hematological, hepatic, respiratory, cardiovascular, renal, neurological or psychiatric disease, gall bladder removal, or current or recurrent disease that could affect the action, absorption, or disposition of the investigational product, or clinical or laboratory assessments.
Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures.
Known or suspected intolerance or hypersensitivity to the investigational product(s), closely-related compounds, or any of the stated ingredients.
Significant illness, as judged by the investigator, within 2 weeks of the first dose of investigational product.
Known history of alcohol or other substance abuse within the last year.
Donation of blood or blood products (Example (eg), plasma or platelets) within 60 days prior to receiving the first dose of investigational product.

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Use of the following prior to administration of investigational product within:
30 days - loop diuretics, lithium, antacids, systemic corticosteroids (medical judgment is required by the investigator. Primarily high doses of systemic corticosteroids [eg, prednisone] should be excluded. Stable doses of hydrocortisone [eg, 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.
Confirmed systolic blood pressure (BP) >39 millimeter of mercury (mmHg) or <89 mmHg, and diastolic BP >89 mmHg or <49 mmHg.
Twelve-lead ECG demonstrating measure of time between the start of the Q wave and the end of the T wave using Fridericia's formula in an electrocardiogram (QTcF) >450 milliseconds (msec) at screening. If QTcF exceeds 450 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF values should be used to determine the subject's eligibility.
Positive screen for drugs of abuse at screening or drugs of abuse or alcohol on Day -1.
Male subjects who consume more than 21 units of alcohol per week or 3 units per day. Female subjects who consume more than 14 units of alcohol per week or 2 units per day. (1 alcohol unit=1 beer or 1 wine (5 ounce (oz) per 150 milliliter (mL)) or 1 liquor (1.5oz/40 mL) or 0.75 oz alcohol).
Positive human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody screen.
Use of tobacco in any form (eg, smoking or chewing) or other nicotine-containing products in any form (eg, gum, patch). Ex-users must report that they have stopped using tobacco for at least 30 days prior to receiving the first dose of investigational product.
Routine consumption of more than 2 units of caffeine per day or subjects who experience caffeine withdrawal headaches. (1 caffeine unit is contained in the following items: one 6 oz (180 mL) cup of coffee, two 12 oz (360 mL) cans of cola, one 12 oz cup of tea, three 1 oz (85 g) chocolate bars. Decaffeinated coffee, tea, or cola are not considered to contain caffeine).
Prior screen failure, randomization, participation, or enrollment in this study or prior exposure to any exogenous PTH, PTH fragments or analogs.
Current use of any medication (including over-the-counter, herbal, or homeopathic preparations; with the exception of hormonal replacement therapy or hormonal contraceptives and occasional use of ibuprofen and acetaminophen). Current use is defined as use within 14 days of the first dose of investigational product.
History of abnormalities of calcium homeostasis including hyperparathyroidism, hypoparathyroidism, hyperthyroidism, osteoporosis, Cushing's syndrome, hypercalcemia, hypocalcemia, or any other calcium disorder.

Trial locations and contacts

1 site in 1 country.

United States1 site

Glendale Adventist Medical Center
Glendale, California, 91206

Other trials in United States

About this study

Official title: A Phase 1, Open-label, Randomized, Cross-over Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of a Single Dose of rhPTH(1-84) Administered Subcutaneously in Japanese Healthy Subjects Compared With Matched Non-Hispanic, Caucasian Healthy Adult Subjects and to Assess Dose Proportionality of 3 Doses of rhPTH(1-84) in the Japanese Subjects

The purpose of this study is to compare how rhPTH(1-84) affects the body between healthy adults of Japanese descent and matched, healthy Caucasian adults.

Conditions: Hypoparathyroidism
Being tested: 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.

rhPTH(1-84)Drug
25 mcg rhPTH(1-84) SC injection
rhPTH(1-84)Drug
50 mcg rhPTH(1-84) SC injection
rhPTH(1-84)Drug
100 mcg rhPTH(1-84) SC injection

Study groups in NCT03150108
Study group	Role	What they receive
Non-Hispanic Caucasians	Experimental	Subjects will receive single dose of 100 microgram (mcg) rhPTH(1-84) subcutaneous (SC) injection on Day 1. Receives: Drug: rhPTH(1-84)
Participants of Japanese Descent	Experimental	Subjects will receive single dose of 100 mcg rhPTH(1-84) SC injection on Day 1; On days 4 and 7, either 25 mcg or 50 mcg SC injection. A washout period of 73 hours will be maintained between each single doses (100 mcg, 50 mcg and 25 mcg) in a cross-over fashion. Receives: Drug: rhPTH(1-84)

What is being measured

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

Baseline-adjusted Cmax of PTH(1-84)
Baseline-adjusted maximum observed drug concentration (Cmax) of PTH(1-84) in plasma was reported. The dispersion measure Geometric Coefficient of Variation was reported in percent (%).
Measured: 30 and 90 minutes (min) Pre-dose, 10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hours (h) Post-dose
Baseline-adjusted Tmax of PTH(1-84)
Baseline-adjusted time to reach maximum observed drug concentration (Tmax) of PTH(1-84) in plasma was reported.
Measured: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
Baseline-adjusted AUC(Last) of PTH(1-84) in Plasma
Baseline-adjusted area under the curve from the time of dosing to the last measurable concentration (AUC(last)) of PTH(1-84) was reported. The dispersion measure Geometric Coefficient of Variation was reported in percent (%).
Measured: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
Baseline-adjusted AUC(0-8) of PTH(1-84) in Plasma
Baseline-adjusted area under the concentration versus time curve from the time of dosing to 8 hours post dose (AUC(0-8)) of PTH(1-84) was reported. The dispersion measure Geometric Coefficient of Variation was reported in percent (%).
Measured: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
Baseline-adjusted AUC(0-inf) of PTH(1-84) in Plasma
Baseline-adjusted area under the concentration versus time curve extrapolated to infinity (AUC(0-inf)) of PTH(1-84) was reported. The dispersion measure Geometric Coefficient of Variation was reported in percent (%).
Measured: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
Baseline- Adjusted % of AUC(0-Inf) Extra of PTH(1-84) in Plasma
Baseline-adjusted % of AUC extrapolated from the last measurable concentration to infinity over (AUC(0-Inf)) of PTH(1-84) in plasma was reported. The dispersion measure Geometric Coefficient of Variation was reported in percent (%).
Measured: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
Baseline-adjusted Lambda_z of PTH(1-84) in Plasma
Baseline-adjusted Lambda z associated with the terminal (log-linear) portion of the curve for PTH(1-84) in plasma was reported. The dispersion measure Geometric Coefficient of Variation was reported in percent (%).
Measured: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
Baseline-adjusted t1/2 of PTH(1-84) in Plasma
Baseline-adjusted Terminal Half-life (t1/2) of PTH(1-84) in plasma was reported.
Measured: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
Baseline-adjusted CL/F of PTH(1-84) in Plasma
Baseline-adjusted apparent clearance (CL/F) of PTH(1-84) in plasma was reported. The dispersion measure Geometric Coefficient of Variation was reported in percent (%).
Measured: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
Baseline-adjusted Vdz/F of PTH(1-84) in Plasma
Baseline-adjusted apparent volume of distribution (Vdz/F) of PTH(1-84) in plasma was reported. The dispersion measure Geometric Coefficient of Variation was reported in percent (%).
Measured: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose

Secondary outcomes (11)

Original Cmax of PTH(1-84) in Plasma
Original maximum observed drug concentration (Cmax) of PTH(1-84) in plasma was reported. The dispersion measure Geometric Coefficient of Variation was reported in percent (%).
Measured: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
Original Tmax of PTH(1-84)
The original time to reach maximum observed drug concentration (Tmax) of PTH(1-84) in plasma was reported.
Measured: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
Original AUClast of PTH(1-84) in Plasma
Original area under the curve from the time of dosing to the last measurable concentration (AUClast) of PTH(1-84) was reported. The dispersion measure Geometric Coefficient of Variation was reported in percent (%).
Measured: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
AUClast of Albumin-corrected Calcium, Serum Total Calcium and Phosphate Levels After Intake of PTH(1-84)
Area under the curve from the time of dosing to the last measurable concentration of albumin-corrected calcium, serum total calcium and phosphate levels after intake of PTH(1-84) was reported. The dispersion measure Geometric Coefficient of Variation was reported in percent (%).
Measured: Non-Hispanic Caucasians: 30 mins predose, 4, 8 and 12 h (Day 1),24 h (Day 2) Japanese Descents: 30 mins predose, 4, 8 and 12 h (Days 1, 4, 7), 24 h (Days 2, 5, 8)
TEmax After Intake of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels
The time to maximum effect (TEmax) of PTH(1-84) on albumin-corrected calcium, serum total calcium and serum phosphate levels were reported.
Measured: Non-Hispanic Caucasians: 30 mins predose, 4, 8 and 12 h (Day 1),24 h (Day 2) Japanese Descents: 30 mins predose, 4, 8 and 12 h (Days 1, 4, 7), 24 h (Days 2, 5, 8)
Emax of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels
The maximum effect (Emax) of PTH(1-84) on albumin-corrected calcium, serum total calcium and serum phosphate levels were reported. The dispersion measure Geometric Coefficient of Variation was reported in percent (%).
Measured: Non-Hispanic Caucasians: 30 mins predose, 4, 8 and 12 h (Day 1),24 h (Day 2) Japanese Descents: 30 mins predose, 4, 8 and 12 h (Days 1, 4, 7), 24 h (Days 2, 5, 8)
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment.
Measured: From start of study drug administration to follow-up (up to 40 days)
Number of Participants With Clinically Significant Changes in Clinical Laboratory Tests Reported as Treatment-emergent Adverse Events (TEAEs)
Clinical laboratory tests included hematology, chemistry, and urinalysis. Number of participants with clinically significant changes in clinical laboratory tests reported as TEAEs were reported.
Measured: Non-Hispanic Caucasians: 30 min pre-dose,24 h,32 days post-dose Japanese Descents: 30 min pre-dose,24 h post-dose on Days 1,4,7 and 32 days after last dose
Number of Participants With Clinically Significant Changes in Vital Signs Reported as Treatment-emergent Adverse Events (TEAEs)
Vital signs were obtained while participant was supine. Vital signs included hematology, chemistry, and urinalysis. Number of participants with clinically significant changes in vital signs reported as TEAEs were reported.
Measured: Non-Hispanic Caucasians: 30 min pre-dose,1,4,8,24 h,32 days post-dose Japanese Descents: 30 min pre-dose,1,4,8,24 h post-dose on Days 1,4,7 and 32 days after last dose
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Results Reported as Treatment-emergent Adverse Events (TEAEs)
Twelve-lead ECGs were performed in triplicate at each time point. For numeric ECG variables, the mean of the valid values at each time point was taken. Number of participants with clinically significant changes in ECGs reported as TEAEs were reported.
Measured: Non-Hispanic Caucasians: 30 min pre-dose,24 h,32 days post-dose Japanese Descents: 30 min pre-dose,24 h post-dose on Days 1,4,7 and 32 days after last dose
Number of Participants Who Reported Positive to Anti-Parathyroid Hormone Antibodies
Number of participants who reported positive to anti-parathyroid hormone antibodies were reported.
Measured: Non-Hispanic Caucasians: 30 min pre-dose,32 days post-dose Japanese Descents: 30 min pre-dose on Days 1,4,7 and 32 days after last dose

Timeline

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

16 May 201726 Jun 2017

First posted12 May 2017
Study start16 May 2017
Primary completion26 Jun 2017
Study completion26 Jun 2017

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: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03150108
Sponsor's protocol ID: SHP634-102
Status last verified: May 2021
First submitted: 1 May 2017
Last updated: 8 Jun 2021
Results posted: Yes, on ClinicalTrials.gov
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 8 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Open-label, Randomized, Cross-over Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of a Single Dose of rhPTH(1-84) Administered Subcutaneously in Japanese Healthy Subjects Compared With Matched Non-Hispanic, Caucasian Healthy Adult Subjects and to Assess Dose Proportionality of 3 Doses of rhPTH(1-84) in the Japanese Subjects
ClinicalTrials.gov ID: NCT03150108
Acronym / sponsor ID: SHP634-102
Conditions: Hypoparathyroidism
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: ShireIndustry (pharma, biotech, devices)
Study start: 16 May 2017 (actual)
Primary completion: 26 Jun 2017 (actual)
Study completion: 26 Jun 2017 (actual)
First posted: 12 May 2017 (actual)
Results: Posted 12 Jul 2019

Clinical summary

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

The purpose of this study is to compare how rhPTH(1-84) affects the body between healthy adults of Japanese descent and matched, healthy Caucasian adults.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Non-Hispanic Caucasians	Experimental	Drug: rhPTH(1-84)Subjects will receive single dose of 100 microgram (mcg) rhPTH(1-84) subcutaneous (SC) injection on Day 1.
Participants of Japanese Descent	Experimental	Drug: rhPTH(1-84)Subjects will receive single dose of 100 mcg rhPTH(1-84) SC injection on Day 1; On days 4 and 7, either 25 mcg or 50 mcg SC injection. A washout period of 73 hours will be maintained between each single doses (100 mcg, 50 mcg and 25 mcg) in a cross-over fashion.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

Ability to voluntarily provide written, signed, and dated informed consent as applicable to participate in the study.
An understanding, ability, and willingness to fully comply with study procedures and restrictions.
Age 18-65 inclusive at the time of consent. The date of signature of the informed consent is defined as the beginning of the screening period. This inclusion criterion will only be assessed at the first screening visit.
Subjects must be either:
Male or nonpregnant, nonlactating female who agrees to comply with any applicable contraceptive requirements of the protocol or females of nonchildbearing potential.

Key exclusion criteria (22 listed)

History of any hematological, hepatic, respiratory, cardiovascular, renal, neurological or psychiatric disease, gall bladder removal, or current or recurrent disease that could affect the action, absorption, or disposition of the investigational product, or clinical or laboratory assessments.
Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures.
Known or suspected intolerance or hypersensitivity to the investigational product(s), closely-related compounds, or any of the stated ingredients.
Significant illness, as judged by the investigator, within 2 weeks of the first dose of investigational product.
Known history of alcohol or other substance abuse within the last year.

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
rhPTH(1-84)25 mcg rhPTH(1-84) SC injection	Drug	Participants of Japanese Descent
rhPTH(1-84)50 mcg rhPTH(1-84) SC injection	Drug	Participants of Japanese Descent
rhPTH(1-84)100 mcg rhPTH(1-84) SC injection	Drug	Non-Hispanic Caucasians

Primary outcome

Baseline-adjusted Cmax of PTH(1-84)
Time frame: 30 and 90 minutes (min) Pre-dose, 10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hours (h) Post-dose
Baseline-adjusted maximum observed drug concentration (Cmax) of PTH(1-84) in plasma was reported. The dispersion measure Geometric Coefficient of Variation was reported in percent (%).
Baseline-adjusted Tmax of PTH(1-84)
Time frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
Baseline-adjusted time to reach maximum observed drug concentration (Tmax) of PTH(1-84) in plasma was reported.
Baseline-adjusted AUC(Last) of PTH(1-84) in Plasma
Time frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
Baseline-adjusted area under the curve from the time of dosing to the last measurable concentration (AUC(last)) of PTH(1-84) was reported. The dispersion measure Geometric Coefficient of Variation was reported in percent (%).
Baseline-adjusted AUC(0-8) of PTH(1-84) in Plasma
Time frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
Baseline-adjusted area under the concentration versus time curve from the time of dosing to 8 hours post dose (AUC(0-8)) of PTH(1-84) was reported. The dispersion measure Geometric Coefficient of Variation was reported in percent (%).
Baseline-adjusted AUC(0-inf) of PTH(1-84) in Plasma
Time frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
Baseline-adjusted area under the concentration versus time curve extrapolated to infinity (AUC(0-inf)) of PTH(1-84) was reported. The dispersion measure Geometric Coefficient of Variation was reported in percent (%).
Baseline- Adjusted % of AUC(0-Inf) Extra of PTH(1-84) in Plasma
Time frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
Baseline-adjusted % of AUC extrapolated from the last measurable concentration to infinity over (AUC(0-Inf)) of PTH(1-84) in plasma was reported. The dispersion measure Geometric Coefficient of Variation was reported in percent (%).
Baseline-adjusted Lambda_z of PTH(1-84) in Plasma
Time frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
Baseline-adjusted Lambda z associated with the terminal (log-linear) portion of the curve for PTH(1-84) in plasma was reported. The dispersion measure Geometric Coefficient of Variation was reported in percent (%).
Baseline-adjusted t1/2 of PTH(1-84) in Plasma
Time frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
Baseline-adjusted Terminal Half-life (t1/2) of PTH(1-84) in plasma was reported.
Baseline-adjusted CL/F of PTH(1-84) in Plasma
Time frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
Baseline-adjusted apparent clearance (CL/F) of PTH(1-84) in plasma was reported. The dispersion measure Geometric Coefficient of Variation was reported in percent (%).
Baseline-adjusted Vdz/F of PTH(1-84) in Plasma
Time frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
Baseline-adjusted apparent volume of distribution (Vdz/F) of PTH(1-84) in plasma was reported. The dispersion measure Geometric Coefficient of Variation was reported in percent (%).

11 secondary outcomes

Original Cmax of PTH(1-84) in Plasma
Time frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
Original Tmax of PTH(1-84)
Time frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
Original AUClast of PTH(1-84) in Plasma
Time frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose
AUClast of Albumin-corrected Calcium, Serum Total Calcium and Phosphate Levels After Intake of PTH(1-84)
Time frame: Non-Hispanic Caucasians: 30 mins predose, 4, 8 and 12 h (Day 1),24 h (Day 2) Japanese Descents: 30 mins predose, 4, 8 and 12 h (Days 1, 4, 7), 24 h (Days 2, 5, 8)
TEmax After Intake of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels
Time frame: Non-Hispanic Caucasians: 30 mins predose, 4, 8 and 12 h (Day 1),24 h (Day 2) Japanese Descents: 30 mins predose, 4, 8 and 12 h (Days 1, 4, 7), 24 h (Days 2, 5, 8)
Emax of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels
Time frame: Non-Hispanic Caucasians: 30 mins predose, 4, 8 and 12 h (Day 1),24 h (Day 2) Japanese Descents: 30 mins predose, 4, 8 and 12 h (Days 1, 4, 7), 24 h (Days 2, 5, 8)
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: From start of study drug administration to follow-up (up to 40 days)
Number of Participants With Clinically Significant Changes in Clinical Laboratory Tests Reported as Treatment-emergent Adverse Events (TEAEs)
Time frame: Non-Hispanic Caucasians: 30 min pre-dose,24 h,32 days post-dose Japanese Descents: 30 min pre-dose,24 h post-dose on Days 1,4,7 and 32 days after last dose
Number of Participants With Clinically Significant Changes in Vital Signs Reported as Treatment-emergent Adverse Events (TEAEs)
Time frame: Non-Hispanic Caucasians: 30 min pre-dose,1,4,8,24 h,32 days post-dose Japanese Descents: 30 min pre-dose,1,4,8,24 h post-dose on Days 1,4,7 and 32 days after last dose
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Results Reported as Treatment-emergent Adverse Events (TEAEs)
Time frame: Non-Hispanic Caucasians: 30 min pre-dose,24 h,32 days post-dose Japanese Descents: 30 min pre-dose,24 h post-dose on Days 1,4,7 and 32 days after last dose
Number of Participants Who Reported Positive to Anti-Parathyroid Hormone Antibodies
Time frame: Non-Hispanic Caucasians: 30 min pre-dose,32 days post-dose Japanese Descents: 30 min pre-dose on Days 1,4,7 and 32 days after last dose

Results and safety

Results posted to the registry on 12 Jul 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Non-Hispanic Caucasians	12	12
Participants of Japanese Descent	12	12

Primary outcome: Baseline-adjusted Cmax of PTH(1-84)

Time frame: 30 and 90 minutes (min) Pre-dose, 10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hours (h) Post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: Picogram per milliliter (pg/mL)

Measure	Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) n = 12	Participants of Japanese Descent: 100 mcg rhPTH(1-84) n = 12	Participants of Japanese Descent: 50 mcg rhPTH(1-84) n = 12	Participants of Japanese Descent: 25 mcg rhPTH(1-84) n = 12
Value	295.662 (41.66)	330.820 (29.44)	175.468 (35.29)	99.708 (22.02)

Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) vs Participants of Japanese Descent: 100 mcg rhPTH(1-84): Geometric mean ratio: 1.119 (90% CI 0.875 to 1.430)
Participants of Japanese Descent: 100 mcg rhPTH(1-84) vs Participants of Japanese Descent: 50 mcg rhPTH(1-84) vs Participants of Japanese Descent: 25 mcg rhPTH(1-84): Increase in Cmax per Dose Doubling: 1.76 (90% CI 1.52 to 2.03)

Population analysed: The pharmacokinetic (PK) set consisted of participants who received at least 1 dose of rhPTH(1-84) and had at least 1 evaluable post-dose PK concentration value.

Primary outcome: Baseline-adjusted Tmax of PTH(1-84)

Time frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose. Median (Full Range). Unit: Hour (h)

Measure	Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) n = 12	Participants of Japanese Descent: 100 mcg rhPTH(1-84) n = 12	Participants of Japanese Descent: 50 mcg rhPTH(1-84) n = 12	Participants of Japanese Descent: 25 mcg rhPTH(1-84) n = 12
Value	0.415 (0.17 to 3.00)	1.000 (0.17 to 4.00)	1.385 (0.50 to 2.50)	1.240 (0.17 to 2.00)

Population analysed: The PK set consisted of participants who received at least 1 dose of rhPTH(1-84) and had at least 1 evaluable post-dose PK concentration value.

Primary outcome: Baseline-adjusted AUC(Last) of PTH(1-84) in Plasma

Time frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: Hour*picogram per milliliter (h*pg/mL)

Measure	Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) n = 12	Participants of Japanese Descent: 100 mcg rhPTH(1-84) n = 12	Participants of Japanese Descent: 50 mcg rhPTH(1-84) n = 12	Participants of Japanese Descent: 25 mcg rhPTH(1-84) n = 12
Value	1037.63 (31.0)	1027.81 (32.6)	602.06 (30.6)	255.67 (28.7)

Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) vs Participants of Japanese Descent: 100 mcg rhPTH(1-84): Geometric mean ratio: 0.99 (90% CI 0.80 to 1.23)
Participants of Japanese Descent: 100 mcg rhPTH(1-84) vs Participants of Japanese Descent: 50 mcg rhPTH(1-84) vs Participants of Japanese Descent: 25 mcg rhPTH(1-84): Increase in AUClast per Dose Doubling: 2.35 (90% CI 2.06 to 2.70)

Population analysed: The PK set consisted of participants who received at least 1 dose of rhPTH(1-84) and had at least 1 evaluable post-dose PK concentration value.

Primary outcome: Baseline-adjusted AUC(0-8) of PTH(1-84) in Plasma

Time frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: h*pg/mL

Measure	Non-Hispanic Caucasians:100 mcg rhPTH(1-84) n = 12	Participants of Japanese Descent: 100 mcg rhPTH(1-84) n = 12	Participants of Japanese Descent: 50 mcg rhPTH(1-84) n = 12	Participants of Japanese Descent: 25 mcg rhPTH(1-84) n = 12
Value	956.63 (32.8)	1033.62 (31.4)	554.23 (30.8)	248.38 (19.7)

Non-Hispanic Caucasians:100 mcg rhPTH(1-84) vs Participants of Japanese Descent: 100 mcg rhPTH(1-84): Geometric mean ratio: 1.08 (90% CI 0.87 to 1.35)
Participants of Japanese Descent: 100 mcg rhPTH(1-84) vs Participants of Japanese Descent: 50 mcg rhPTH(1-84) vs Participants of Japanese Descent: 25 mcg rhPTH(1-84): Increase in AUC0-8 per Dose Doubling: 2.23 (90% CI 1.98 to 2.51)

Population analysed: The PK set consisted of participants who received at least 1 dose of rhPTH(1-84) and had at least 1 evaluable post-dose PK concentration value.

11 secondary outcomes are reported in the full results.

Adverse events

Time frame: From start of study drug administration to follow-up (up to 40 days). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Non-Hispanic Caucasians:100 mcg rhPTH(1- 84)	0 of 12 (0%)	4 of 12 (33.3%)	0 of 12
Participants of Japanese Descent: 100 mcg rhPTH(1-84)	0 of 12 (0%)	6 of 12 (50%)	0 of 12
Participants of Japanese Descent: 50 mcg rhPTH(1-84)	0 of 12 (0%)	1 of 12 (8.3%)	0 of 12
Participants of Japanese Descent: 25 mcg rhPTH(1-84)	0 of 12 (0%)	3 of 12 (25%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 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

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing rhPTH(1-84) in people with Hypoparathyroidism, run by Shire at 1 site in United States.

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 22 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 8 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 12 Jul 2019). 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?

Baseline-adjusted Cmax of PTH(1-84) (time frame: 30 and 90 minutes (min) Pre-dose, 10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hours (h) Post-dose). The study lists 10 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 NCT03150108.

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 8 Jun 2021.