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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Non-Hispanic Caucasians | Experimental | Subjects will receive single dose of 100 microgram (mcg) rhPTH(1-84) subcutaneous (SC) injection on Day 1. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rhPTH(1-84) | Drug | 25 mcg rhPTH(1-84) SC injection |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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 (%). | 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. | 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 (%). | 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 (%). | 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 (%). | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 (%). | 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 |
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Inclusion Criteria:
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.
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.
Exclusion Criteria:
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.
Use of the following prior to administration of investigational product within:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Glendale Adventist Medical Center | Glendale | California | 91206 | United States |
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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IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
A total of 24 participants (12 non-Hispanic healthy volunteer Caucasian participants and 12 healthy Japanese participants) were enrolled and randomized to study treatment.
The study was conducted at a single center in United States between 19 April 2017 (first participant first visit) and 26 Jun 2017 (last participant last visit).
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| ID | Title | Description |
|---|---|---|
| FG000 | Non-Hispanic Caucasians | Participants (who have 2 non-Hispanic Caucasian parents and 4 non-Hispanic Caucasian grandparents) matched to participants of Japanese descent based on sex (1:1 male: female), age (+/-7 years), and body mass index (+/-15%) received a single subcutaneous (SC) injection of 100 microgram (mcg) recombinant human parathyroid hormone (rhPTH[1-84]) on Day 1. |
| FG001 | Participants of Japanese Descent | Participants (born in Japan, who have resided outside of Japan for no longer than 5 years and were of Japanese parentage, defined as having 2 Japanese parents, and 4 Japanese grandparents, all born in Japan) received a single SC injection of 100 mcg rhPTH(1-84) on Day 1, then followed by either 25 mcg or 50 mcg SC injection on Days 4 and 7 in a cross-over fashion. A washout period of 73 hours was maintained between each single doses (100 mcg, 50 mcg and 25 mcg). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Safety set included enrolled participants who received at least 1 dose of rhPTH(1-84).
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| ID | Title | Description |
|---|---|---|
| BG000 | Non-Hispanic Caucasians | Participants (who have 2 non-Hispanic Caucasian parents and 4 non-Hispanic Caucasian grandparents) matched to participants of Japanese descent based on sex (1:1 male: female), age (+/-7 years), and body mass index (+/-15%) received a single SC injection of 100 mcg rhPTH[1-84] on Day 1. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 (%). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Picogram per milliliter (pg/mL) | 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 |
|
From start of study drug administration to follow-up (up to 40 days)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Non-Hispanic Caucasians:100 mcg rhPTH(1- 84) | Participants received a single SC injection of 100 mcg rhPTH(1-84) on Day 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol: Original | Jan 29, 2017 | Apr 30, 2019 | Prot_000.pdf |
| Prot | Yes | No | No | Study Protocol: Amendment 1 | Mar 21, 2017 | Apr 30, 2019 | Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 12, 2017 | Apr 30, 2019 | SAP_002.pdf |
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| ID | Term |
|---|---|
| D007011 | Hypoparathyroidism |
| ID | Term |
|---|---|
| D010279 | Parathyroid Diseases |
| D004700 | Endocrine System Diseases |
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| rhPTH(1-84) |
| Drug |
50 mcg rhPTH(1-84) SC injection |
|
| rhPTH(1-84) | Drug | 100 mcg rhPTH(1-84) SC injection |
|
| 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 (%). | 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 (%). | 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. | 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 (%). | 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 (%). | 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. |
| 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 (%). | 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 (%). | 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. | 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 (%). | 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. | 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. | 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. | 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. | 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. | 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 |
| Participants of Japanese Descent |
Participants (born in Japan, who have resided outside of Japan for no longer than 5 years and were of Japanese parentage, defined as having 2 Japanese parents, and 4 Japanese grandparents, all born in Japan) received a single SC injection of 100 mcg rhPTH(1-84) on Day 1, then followed by either 25 mcg or 50 mcg SC injection on Days 4 and 7 in a cross-over fashion. A washout period of 73 hours was maintained between each single doses (100 mcg, 50 mcg and 25 mcg). |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Participants (born in Japan, who have resided outside of Japan for no longer than 5 years and were of Japanese parentage, defined as having 2 Japanese parents, and 4 Japanese grandparents, all born in Japan) received a single SC injection of 100 mcg rhPTH(1-84) on Day 1. |
| OG002 | Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Participants (born in Japan, who have resided outside of Japan for no longer than 5 years and were of Japanese parentage, defined as having 2 Japanese parents, and 4 Japanese grandparents, all born in Japan) received a single SC injection of 50 mcg rhPTH(1-84) on Day 4 or 7. |
| OG003 | Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Participants (born in Japan, who have resided outside of Japan for no longer than 5 years and were of Japanese parentage, defined as having 2 Japanese parents, and 4 Japanese grandparents, all born in Japan) received a single SC injection of 25 mcg rhPTH(1-84) on Day 4 or 7. |
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| Primary | 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. | 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. | Posted | Median | Full Range | Hour (h) | 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 |
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| Primary | 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 (%). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*picogram per milliliter (h*pg/mL) | 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 |
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| Primary | 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 (%). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*pg/mL | 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 |
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| Primary | 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 (%). | 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. Here number of participants analyzed indicates the participants evaluable for this outcome. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*pg/mL | 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 |
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| Primary | 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 (%). | 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. Here number of participants analyzed indicates the participants evaluable for this outcome. | Posted | Geometric Mean | Geometric Coefficient of Variation | Percentage of AUC | 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 |
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| Primary | 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 (%). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Per hour (1/h) | 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 |
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| Primary | 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. | 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. Here number of participants analyzed indicates the participants evaluable for this outcome. | Posted | Median | Full Range | Hour (h) | 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 |
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| Primary | 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 (%). | 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. Here number of participants analyzed indicates the participants evaluable for this outcome. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter per hour (L/h) | 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 |
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| Primary | 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 (%). | 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. Here number of participants analyzed indicates the participants evaluable for this outcome. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters (L) | 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 |
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| Secondary | 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 (%). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | pg/mL | 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 |
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| Secondary | Original Tmax of PTH(1-84) | The original time to reach maximum observed drug concentration (Tmax) of PTH(1-84) in plasma was reported. | 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. | Posted | Median | Full Range | Hour (h) | 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 |
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| Secondary | 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 (%). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*pg/mL | 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 |
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| Secondary | 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 (%). | The pharmacodynamic (PD) set consisted of participants who received at least 1 dose of rhPTH(1-84) and had at least 1 evaluable post-dose PD concentration value. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours * millimoles per liter (h×mmol/L) | 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) |
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| Secondary | 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. | The PD set consisted of participants who received at least 1 dose of rhPTH(1-84) and had at least 1 evaluable post-dose PD concentration value. | Posted | Median | Full Range | Hour (h) | 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) |
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| Secondary | 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 (%). | The PD set consisted of participants who received at least 1 dose of rhPTH(1-84) and had at least 1 evaluable post-dose PD concentration value. | Posted | Geometric Mean | Geometric Coefficient of Variation | millimoles per liter (mmol/L) | 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) |
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| Secondary | 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. | The safety set included enrolled participants who received at least 1 dose of rhPTH(1-84). | Posted | Count of Participants | Participants | From start of study drug administration to follow-up (up to 40 days) |
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| Secondary | 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. | The safety set included enrolled participants who received at least 1 dose of rhPTH(1-84). | Posted | Count of Participants | Participants | 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 |
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| Secondary | 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. | The safety set included enrolled participants who received at least 1 dose of rhPTH(1-84). | Posted | Count of Participants | Participants | 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 |
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| Secondary | 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. | The safety set included enrolled participants who received at least 1 dose of rhPTH(1-84). | Posted | Count of Participants | Participants | 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 |
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| Secondary | Number of Participants Who Reported Positive to Anti-Parathyroid Hormone Antibodies | Number of participants who reported positive to anti-parathyroid hormone antibodies were reported. | The safety set included enrolled participants who received at least 1 dose of rhPTH(1-84). | Posted | Count of Participants | Participants | 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 |
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| 0 |
| 12 |
| 0 |
| 12 |
| 4 |
| 12 |
| EG001 | Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Participants received a single SC injection of 100 mcg rhPTH(1-84) on Day 1. | 0 | 12 | 0 | 12 | 6 | 12 |
| EG002 | Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Participants received a single SC injection of 50 mcg rhPTH(1-84) on Day 4 or 7. | 0 | 12 | 0 | 12 | 1 | 12 |
| EG003 | Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Participants received a single SC injection of 25 mcg rhPTH(1-84) on Day 4 or 7. | 0 | 12 | 0 | 12 | 3 | 12 |
| Vomiting | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
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| Sunburn | Injury, poisoning and procedural complications | MedDRA 20.0 | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 20.0 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 20.0 | Non-systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 20.0 | Non-systematic Assessment |
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| Fatigue | General disorders | MedDRA 20.0 | Non-systematic Assessment |
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| Influenza like illness | General disorders | MedDRA 20.0 | Non-systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Non-systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Non-systematic Assessment |
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If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Dose proportionality was assessed for baseline-adjusted AUClast using the power model. The power model assumes a linear relationship between the natural log transformed parameter and the natural log transformed dose. The fold increase in PK parameters with doubling the dose and the 90% CIs were calculated. |
| Increase in AUClast per Dose Doubling |
| 2.35 |
| 90 |
| 2.06 |
| 2.70 |
Linear model of log transformed PK parameters at all doses in Japanese descent, including log transformed dose, period, sequence as fixed effects, and intercept as a random effect accounting for each participant within sequence as their own control. |
| Other |
Dose proportionality |
Dose proportionality was assessed for baseline-adjusted AUC0-8 using the power model. The power model assumes a linear relationship between the natural log transformed parameter and the natural log transformed dose. The fold increase in PK parameters with doubling the dose and the 90% CIs were calculated. |
| Increase in AUC0-8 per Dose Doubling |
| 2.23 |
| 2-Sided |
| 90 |
| 1.98 |
| 2.51 |
Linear model of log transformed PK parameters at all doses in Japanese descent, including log transformed dose, period, sequence as fixed effects, and intercept as a random effect accounting for each participant within sequence as their own control. |
| Other |
Dose proportionality |
Dose proportionality was assessed for baseline-adjusted AUC0-inf using the power model. The power model assumes a linear relationship between the natural log transformed parameter and the natural log transformed dose. The fold increase in PK parameters with doubling the dose and the 90% CIs were calculated. |
| Increase in AUC0-inf per Dose Doubling |
| 2.31 |
| 2-Sided |
| 90 |
| 1.96 |
| 2.71 |
Linear model of log transformed PK parameters at all doses in Japanese descent, including log transformed dose, period, sequence as fixed effects, and intercept as a random effect accounting for each participant within sequence as their own control. |
| Other |
Dose proportionality |
| Serum Total Calcium |
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| Serum Phosphate |
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| Serum Total Calcium |
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| Serum Phosphate |
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| Serum Total Calcium |
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| Serum Phosphate |
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