Hypoparathyroidism
Conditions
Brief 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.
Interventions
DRUGrhPTH(1-84)
25 mcg rhPTH(1-84) SC injection
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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: * 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. * 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: * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline-adjusted Cmax of PTH(1-84) | 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) | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 (%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Original Cmax of PTH(1-84) in Plasma | 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 maximum observed drug concentration (Cmax) of PTH(1-84) in plasma was reported. The dispersion measure Geometric Coefficient of Variation was reported in percent (%). |
| Number of Participants Who Reported Positive to Anti-Parathyroid Hormone Antibodies | 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 | Number of participants who reported positive to anti-parathyroid hormone antibodies were reported. |
| Original Tmax of PTH(1-84) | 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 | The original time to reach maximum observed drug concentration (Tmax) of PTH(1-84) in plasma was reported. |
| Original AUClast of PTH(1-84) in Plasma | 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 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 (%). |
| AUClast of Albumin-corrected Calcium, Serum Total Calcium and Phosphate Levels After Intake of PTH(1-84) | 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) | 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 (%). |
| TEmax After Intake of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | 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) | The time to maximum effect (TEmax) of PTH(1-84) on albumin-corrected calcium, serum total calcium and serum phosphate levels were reported. |
| Emax of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | 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) | 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 (%). |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From start of study drug administration to follow-up (up to 40 days) | 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. |
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Tests Reported as Treatment-emergent Adverse Events (TEAEs) | 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 | Clinical laboratory tests included hematology, chemistry, and urinalysis. Number of participants with clinically significant changes in clinical laboratory tests reported as TEAEs were reported. |
| Number of Participants With Clinically Significant Changes in Vital Signs Reported as Treatment-emergent Adverse Events (TEAEs) | 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 | 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. |
| Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Results Reported as Treatment-emergent Adverse Events (TEAEs) | 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 | 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. |
Countries
United States
Participant flow
Recruitment details
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).
Pre-assignment details
A total of 24 participants (12 non-Hispanic healthy volunteer Caucasian participants and 12 healthy Japanese participants) were enrolled and randomized to study treatment.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 12 |
| 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). | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Participants of Japanese Descent | Total | Non-Hispanic Caucasians |
|---|---|---|---|
| Age, Continuous | 41.3 Years STANDARD_DEVIATION 10.4 | 40.8 Years STANDARD_DEVIATION 9.53 | 40.3 Years STANDARD_DEVIATION 9.01 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 24 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 12 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 12 Participants | 12 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 10 Participants | 20 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 4 / 12 | 6 / 12 | 1 / 12 | 3 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
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 (%).
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | Baseline-adjusted AUC(0-8) of PTH(1-84) in Plasma | 956.63 h*pg/mL | Geometric Coefficient of Variation 32.8 |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Baseline-adjusted AUC(0-8) of PTH(1-84) in Plasma | 1033.62 h*pg/mL | Geometric Coefficient of Variation 31.4 |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Baseline-adjusted AUC(0-8) of PTH(1-84) in Plasma | 554.23 h*pg/mL | Geometric Coefficient of Variation 30.8 |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Baseline-adjusted AUC(0-8) of PTH(1-84) in Plasma | 248.38 h*pg/mL | Geometric Coefficient of Variation 19.7 |
90% CI: [0.87, 1.35]
Comparison: 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.90% CI: [1.98, 2.51]
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 (%).
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | Baseline-adjusted AUC(0-inf) of PTH(1-84) in Plasma | 1028.29 h*pg/mL | Geometric Coefficient of Variation 37 |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Baseline-adjusted AUC(0-inf) of PTH(1-84) in Plasma | 1039.34 h*pg/mL | Geometric Coefficient of Variation 29.8 |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Baseline-adjusted AUC(0-inf) of PTH(1-84) in Plasma | 589.25 h*pg/mL | Geometric Coefficient of Variation 31.6 |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Baseline-adjusted AUC(0-inf) of PTH(1-84) in Plasma | 249.51 h*pg/mL | Geometric Coefficient of Variation 21.9 |
90% CI: [0.77, 1.33]
Comparison: 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.90% CI: [1.96, 2.71]
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 (%).
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | Baseline-adjusted AUC(Last) of PTH(1-84) in Plasma | 1037.63 Hour*picogram per milliliter (h*pg/mL) | Geometric Coefficient of Variation 31 |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Baseline-adjusted AUC(Last) of PTH(1-84) in Plasma | 1027.81 Hour*picogram per milliliter (h*pg/mL) | Geometric Coefficient of Variation 32.6 |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Baseline-adjusted AUC(Last) of PTH(1-84) in Plasma | 602.06 Hour*picogram per milliliter (h*pg/mL) | Geometric Coefficient of Variation 30.6 |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Baseline-adjusted AUC(Last) of PTH(1-84) in Plasma | 255.67 Hour*picogram per milliliter (h*pg/mL) | Geometric Coefficient of Variation 28.7 |
90% CI: [0.8, 1.23]
Comparison: 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.90% CI: [2.06, 2.7]
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 (%).
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | Baseline-adjusted CL/F of PTH(1-84) in Plasma | 97.25 Liter per hour (L/h) | Geometric Coefficient of Variation 37 |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Baseline-adjusted CL/F of PTH(1-84) in Plasma | 96.22 Liter per hour (L/h) | Geometric Coefficient of Variation 29.8 |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Baseline-adjusted CL/F of PTH(1-84) in Plasma | 84.84 Liter per hour (L/h) | Geometric Coefficient of Variation 31.6 |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Baseline-adjusted CL/F of PTH(1-84) in Plasma | 100.18 Liter per hour (L/h) | Geometric Coefficient of Variation 21.9 |
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 (%).
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | Baseline-adjusted Cmax of PTH(1-84) | 295.662 Picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 41.66 |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Baseline-adjusted Cmax of PTH(1-84) | 330.820 Picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 29.44 |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Baseline-adjusted Cmax of PTH(1-84) | 175.468 Picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 35.29 |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Baseline-adjusted Cmax of PTH(1-84) | 99.708 Picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 22.02 |
90% CI: [0.875, 1.43]
Comparison: Dose proportionality was assessed for baseline-adjusted Cmax 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.90% CI: [1.52, 2.03]
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 (%).
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | Baseline-adjusted Lambda_z of PTH(1-84) in Plasma | 0.4496 Per hour (1/h) | Geometric Coefficient of Variation 67.73 |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Baseline-adjusted Lambda_z of PTH(1-84) in Plasma | 0.6672 Per hour (1/h) | Geometric Coefficient of Variation 35.835 |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Baseline-adjusted Lambda_z of PTH(1-84) in Plasma | 0.5714 Per hour (1/h) | Geometric Coefficient of Variation 65.437 |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Baseline-adjusted Lambda_z of PTH(1-84) in Plasma | 0.8277 Per hour (1/h) | Geometric Coefficient of Variation 57.118 |
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 (%).
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | Baseline- Adjusted % of AUC(0-Inf) Extra of PTH(1-84) in Plasma | 1.416 Percentage of AUC | Geometric Coefficient of Variation 198.59 |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Baseline- Adjusted % of AUC(0-Inf) Extra of PTH(1-84) in Plasma | 0.932 Percentage of AUC | Geometric Coefficient of Variation 330.55 |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Baseline- Adjusted % of AUC(0-Inf) Extra of PTH(1-84) in Plasma | 1.555 Percentage of AUC | Geometric Coefficient of Variation 173.86 |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Baseline- Adjusted % of AUC(0-Inf) Extra of PTH(1-84) in Plasma | 3.015 Percentage of AUC | Geometric Coefficient of Variation 135.99 |
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.
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
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | Baseline-adjusted t1/2 of PTH(1-84) in Plasma | 1.390 Hour (h) |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Baseline-adjusted t1/2 of PTH(1-84) in Plasma | 1.060 Hour (h) |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Baseline-adjusted t1/2 of PTH(1-84) in Plasma | 1.020 Hour (h) |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Baseline-adjusted t1/2 of PTH(1-84) in Plasma | 0.950 Hour (h) |
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.
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
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | Baseline-adjusted Tmax of PTH(1-84) | 0.415 Hour (h) |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Baseline-adjusted Tmax of PTH(1-84) | 1.000 Hour (h) |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Baseline-adjusted Tmax of PTH(1-84) | 1.385 Hour (h) |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Baseline-adjusted Tmax of PTH(1-84) | 1.240 Hour (h) |
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 (%).
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | Baseline-adjusted Vdz/F of PTH(1-84) in Plasma | 216.30 Liters (L) | Geometric Coefficient of Variation 93.9 |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Baseline-adjusted Vdz/F of PTH(1-84) in Plasma | 144.18 Liters (L) | Geometric Coefficient of Variation 54.7 |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Baseline-adjusted Vdz/F of PTH(1-84) in Plasma | 148.50 Liters (L) | Geometric Coefficient of Variation 71.9 |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Baseline-adjusted Vdz/F of PTH(1-84) in Plasma | 121.02 Liters (L) | Geometric Coefficient of Variation 57.7 |
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 (%).
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)
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | AUClast of Albumin-corrected Calcium, Serum Total Calcium and Phosphate Levels After Intake of PTH(1-84) | Albumin-corrected Calcium | 52.94 Hours * millimoles per liter (h×mmol/L) | Geometric Coefficient of Variation 2.5 |
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | AUClast of Albumin-corrected Calcium, Serum Total Calcium and Phosphate Levels After Intake of PTH(1-84) | Serum Phosphate | 27.21 Hours * millimoles per liter (h×mmol/L) | Geometric Coefficient of Variation 10.5 |
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | AUClast of Albumin-corrected Calcium, Serum Total Calcium and Phosphate Levels After Intake of PTH(1-84) | Serum Total Calcium | 54.21 Hours * millimoles per liter (h×mmol/L) | Geometric Coefficient of Variation 2.7 |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | AUClast of Albumin-corrected Calcium, Serum Total Calcium and Phosphate Levels After Intake of PTH(1-84) | Albumin-corrected Calcium | 53.22 Hours * millimoles per liter (h×mmol/L) | Geometric Coefficient of Variation 2.3 |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | AUClast of Albumin-corrected Calcium, Serum Total Calcium and Phosphate Levels After Intake of PTH(1-84) | Serum Phosphate | 28.85 Hours * millimoles per liter (h×mmol/L) | Geometric Coefficient of Variation 10.2 |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | AUClast of Albumin-corrected Calcium, Serum Total Calcium and Phosphate Levels After Intake of PTH(1-84) | Serum Total Calcium | 54.62 Hours * millimoles per liter (h×mmol/L) | Geometric Coefficient of Variation 1.5 |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | AUClast of Albumin-corrected Calcium, Serum Total Calcium and Phosphate Levels After Intake of PTH(1-84) | Serum Total Calcium | 54.12 Hours * millimoles per liter (h×mmol/L) | Geometric Coefficient of Variation 2.6 |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | AUClast of Albumin-corrected Calcium, Serum Total Calcium and Phosphate Levels After Intake of PTH(1-84) | Albumin-corrected Calcium | 52.94 Hours * millimoles per liter (h×mmol/L) | Geometric Coefficient of Variation 2.5 |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | AUClast of Albumin-corrected Calcium, Serum Total Calcium and Phosphate Levels After Intake of PTH(1-84) | Serum Phosphate | 28.60 Hours * millimoles per liter (h×mmol/L) | Geometric Coefficient of Variation 7.8 |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | AUClast of Albumin-corrected Calcium, Serum Total Calcium and Phosphate Levels After Intake of PTH(1-84) | Albumin-corrected Calcium | 52.61 Hours * millimoles per liter (h×mmol/L) | Geometric Coefficient of Variation 3.1 |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | AUClast of Albumin-corrected Calcium, Serum Total Calcium and Phosphate Levels After Intake of PTH(1-84) | Serum Phosphate | 29.57 Hours * millimoles per liter (h×mmol/L) | Geometric Coefficient of Variation 7.6 |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | AUClast of Albumin-corrected Calcium, Serum Total Calcium and Phosphate Levels After Intake of PTH(1-84) | Serum Total Calcium | 53.62 Hours * millimoles per liter (h×mmol/L) | Geometric Coefficient of Variation 3.5 |
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 (%).
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)
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | Emax of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Albumin-corrected Calcium | 2.287 millimoles per liter (mmol/L) | Geometric Coefficient of Variation 2.31 |
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | Emax of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Serum Phosphate | 1.286 millimoles per liter (mmol/L) | Geometric Coefficient of Variation 11.88 |
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | Emax of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Serum Total Calcium | 2.359 millimoles per liter (mmol/L) | Geometric Coefficient of Variation 3.49 |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Emax of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Albumin-corrected Calcium | 2.284 millimoles per liter (mmol/L) | Geometric Coefficient of Variation 2.46 |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Emax of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Serum Phosphate | 1.325 millimoles per liter (mmol/L) | Geometric Coefficient of Variation 11.47 |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Emax of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Serum Total Calcium | 2.347 millimoles per liter (mmol/L) | Geometric Coefficient of Variation 1.83 |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Emax of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Serum Total Calcium | 2.330 millimoles per liter (mmol/L) | Geometric Coefficient of Variation 2.6 |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Emax of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Albumin-corrected Calcium | 2.283 millimoles per liter (mmol/L) | Geometric Coefficient of Variation 3.09 |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Emax of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Serum Phosphate | 1.325 millimoles per liter (mmol/L) | Geometric Coefficient of Variation 7.94 |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Emax of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Albumin-corrected Calcium | 2.282 millimoles per liter (mmol/L) | Geometric Coefficient of Variation 2.34 |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Emax of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Serum Phosphate | 1.383 millimoles per liter (mmol/L) | Geometric Coefficient of Variation 8.06 |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Emax of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Serum Total Calcium | 2.322 millimoles per liter (mmol/L) | Geometric Coefficient of Variation 2.02 |
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.
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
Population: The safety set included enrolled participants who received at least 1 dose of rhPTH(1-84).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | Number of Participants Who Reported Positive to Anti-Parathyroid Hormone Antibodies | 0 Participants |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Number of Participants Who Reported Positive to Anti-Parathyroid Hormone Antibodies | 0 Participants |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Number of Participants Who Reported Positive to Anti-Parathyroid Hormone Antibodies | 0 Participants |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Number of Participants Who Reported Positive to Anti-Parathyroid Hormone Antibodies | 0 Participants |
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.
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
Population: The safety set included enrolled participants who received at least 1 dose of rhPTH(1-84).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | Number of Participants With Clinically Significant Changes in Clinical Laboratory Tests Reported as Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Number of Participants With Clinically Significant Changes in Clinical Laboratory Tests Reported as Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Number of Participants With Clinically Significant Changes in Clinical Laboratory Tests Reported as Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Number of Participants With Clinically Significant Changes in Clinical Laboratory Tests Reported as Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
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.
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
Population: The safety set included enrolled participants who received at least 1 dose of rhPTH(1-84).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Results Reported as Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Results Reported as Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Results Reported as Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Results Reported as Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
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.
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
Population: The safety set included enrolled participants who received at least 1 dose of rhPTH(1-84).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | Number of Participants With Clinically Significant Changes in Vital Signs Reported as Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Number of Participants With Clinically Significant Changes in Vital Signs Reported as Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Number of Participants With Clinically Significant Changes in Vital Signs Reported as Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Number of Participants With Clinically Significant Changes in Vital Signs Reported as Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
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.
Time frame: From start of study drug administration to follow-up (up to 40 days)
Population: The safety set included enrolled participants who received at least 1 dose of rhPTH(1-84).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 Participants |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 1 Participants |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
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 (%).
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | Original AUClast of PTH(1-84) in Plasma | 1685.62 h*pg/mL | Geometric Coefficient of Variation 18.2 |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Original AUClast of PTH(1-84) in Plasma | 1823.70 h*pg/mL | Geometric Coefficient of Variation 23.7 |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Original AUClast of PTH(1-84) in Plasma | 1300.09 h*pg/mL | Geometric Coefficient of Variation 21.7 |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Original AUClast of PTH(1-84) in Plasma | 959.49 h*pg/mL | Geometric Coefficient of Variation 26.1 |
90% CI: [0.93, 1.25]
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 (%).
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | Original Cmax of PTH(1-84) in Plasma | 324.43 pg/mL | Geometric Coefficient of Variation 36.2 |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Original Cmax of PTH(1-84) in Plasma | 365.52 pg/mL | Geometric Coefficient of Variation 27.3 |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Original Cmax of PTH(1-84) in Plasma | 206.05 pg/mL | Geometric Coefficient of Variation 29.6 |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Original Cmax of PTH(1-84) in Plasma | 129.74 pg/mL | Geometric Coefficient of Variation 21.1 |
90% CI: [0.9, 1.4]
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.
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
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | Original Tmax of PTH(1-84) | 0.415 Hour (h) |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | Original Tmax of PTH(1-84) | 1.000 Hour (h) |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | Original Tmax of PTH(1-84) | 1.385 Hour (h) |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | Original Tmax of PTH(1-84) | 1.240 Hour (h) |
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.
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)
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | TEmax After Intake of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Albumin-corrected Calcium | 8.000 Hour (h) |
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | TEmax After Intake of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Serum Phosphate | 8.010 Hour (h) |
| Non-Hispanic Caucasians: 100 mcg rhPTH(1-84) | TEmax After Intake of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Serum Total Calcium | 8.000 Hour (h) |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | TEmax After Intake of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Albumin-corrected Calcium | 8.000 Hour (h) |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | TEmax After Intake of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Serum Phosphate | 8.000 Hour (h) |
| Participants of Japanese Descent: 100 mcg rhPTH(1-84) | TEmax After Intake of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Serum Total Calcium | 8.000 Hour (h) |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | TEmax After Intake of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Serum Total Calcium | 8.000 Hour (h) |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | TEmax After Intake of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Albumin-corrected Calcium | 4.000 Hour (h) |
| Participants of Japanese Descent: 50 mcg rhPTH(1-84) | TEmax After Intake of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Serum Phosphate | 8.000 Hour (h) |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | TEmax After Intake of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Albumin-corrected Calcium | 4.000 Hour (h) |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | TEmax After Intake of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Serum Phosphate | 8.000 Hour (h) |
| Participants of Japanese Descent: 25 mcg rhPTH(1-84) | TEmax After Intake of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels | Serum Total Calcium | 4.000 Hour (h) |