Study of rhPTH(1-84) in Japanese Healthy Subjects Compared With Matched Caucasian Healthy Adult Subjects
Condition: Hypoparathyroidism
MeSH terms: Hypoparathyroidism
Intervention: rhPTH(1-84); rhPTH(1-84); rhPTH(1-84)
Intervention description: 25 mcg rhPTH(1-84) SC injection; 50 mcg rhPTH(1-84) SC injection; 100 mcg rhPTH(1-84) SC injection
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

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.
    

Eligibility criteria:

        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.