A Study of Relative Bioavailability of a New Formulation Compared With the Approved Formulation of rhPTH [1-84] and to Find Out Dose Linearity of the New Formulation in Healthy Adults
Condition: Healthy Volunteers
Intervention: rhPTH(1-84)
Intervention description: Participants in both part I and part II of the study will receive a single SC injection of rhPTH(1-84) depending upon the treatment sequence allocation on Day 1 of each treatment period.
Intervention MeSH terms: Parathyroid Hormone
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 96.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The main aim of Part I of this study is to evaluate the relative bioavailability of a new
      formulation compared with the approved formulation when a single dose of rhPTH(1-84) is given
      to healthy volunteers. Bioavailability is the ability of a drug to be absorbed and used by
      the body. In Part II, the main aim is to assess the dose linearity of the new formulation.

      Participants will receive 2 doses in Part I and 4 doses in Part II.

      Participants need to visit their doctor approximately 14 days and 30 days after the last dose
      of study drug.
    

Eligibility criteria:

        Inclusion Criteria:

        Participants must fulfill all of the following inclusion criteria to be eligible for
        participation in the study:

          -  Healthy, adult, male or female, 18-65 years of age, inclusive, at screening. Attempts
             will be made to enroll at least 20% of each sex in each study part.

          -  Continuous non-smoker who has not used nicotine containing products for at least 90
             days prior to the first dosing and throughout the study, based on participant
             self-reporting.

          -  Body mass index (BMI) greater than or equal to (>=) 18.5 and less than or equal to
             (<=) 30.0 kilogram per square meter (kg/m2) at screening.

          -  Medically healthy with no clinically significant medical history, physical
             examination, laboratory profiles, vital signs or ECGs, as deemed by the Investigator
             or designee including the following:

               -  Serum calcium, parathyroid hormone (PTH), phosphate, and magnesium within
                  laboratory normal limits at screening and check-in.

               -  Vitamin D (1,25(OH)2D3) levels between lower limit of normal and up to 1.5x Upper
                  Limit of Normal (ULN).

               -  Seated blood pressure Beats per minute (bpm) is >= 89/49 millimeters of mercury
                  (mmHg) and <=139/89 mmHg at screening.

               -  Seated pulse rate is >=40 bpm and <=99 bpm at screening.

               -  QTcF interval is <=450 millisecond (msec) (males) or <= 470 msec (females) or ECG
                  findings considered normal or not clinically significant by the Investigator or
                  designee at screening.

               -  Estimated creatinine clearance >= 80 milliliter per minute (mL/minute) at
                  screening.

          -  Agrees to comply with any applicable contraceptive requirements of the protocol.

          -  Understands the study procedures in the ICF, be able to voluntarily provide written,
             signed, and dated informed consent, and be willing and able to comply with the
             protocol.

        Exclusion Criteria:

        Participants must not be enrolled in the study if they meet any of the following criteria:

          -  Mentally or legally incapacitated or has significant emotional problems at the time of
             the screening visit or expected during the conduct of the study in the opinion of the
             Investigator or designee.

          -  History or presence of clinically significant medical or psychiatric condition or
             disease in the opinion of the Investigator or designee.

          -  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 study drug, or
             clinical or laboratory assessments.

          -  Participants who are at increased baseline risk for osteosarcoma such as participants
             with Paget's disease of bone or unexplained elevations of alkaline phosphatase (ALP),
             hereditary disorders predisposing to osteosarcoma or a prior history of external beam
             or implant radiation therapy involving the skeleton.

          -  History of any illness that, in the opinion of the Investigator or designee, might
             confound the results of the study or poses an additional risk to the participant by
             their participation in the study.

          -  History or presence of alcoholism or drug abuse, in the opinion of the Investigator or
             designee, within the past 2 years prior to the first dosing.

          -  Male participants who consume more than 21 units of alcohol per week or 3 units per
             day. Female participants who consume more than 14 units of alcohol per week or 2 units
             per day. (1 alcohol unit=1 beer or 1 wine (5 ounces (oz)/150 in milliliters (mL) or 1
             liquor (1.5 oz/40 mL) or 0.75 oz alcohol).

          -  Positive urine drug or alcohol results at screening or check-in.

          -  History or presence of hypersensitivity or idiosyncratic reaction to the study drug or
             related compounds.

          -  History of abnormalities of calcium homeostasis including hyperparathyroidism,
             hypoparathyroidism, hyperthyroidism, Cushing's syndrome, hypercalcemia, hypocalcemia,
             osteoporosis, or any other calcium disorder.

          -  Female participants who have a positive pregnancy test or who are lactating.

          -  Positive results at screening for human immunodeficiency virus (HIV), hepatitis B
             surface antigen (HBsAg), or hepatitis C virus (HCV).

          -  Has tattoo(s) or scarring at or near the site of injection or any other condition
             which may interfere with injection site examination, in the opinion of the
             Investigator or designee.

          -  Routine consumption of more than 2 units of caffeine per day or participants who
             experience caffeine withdrawal headaches. A unit of caffeine 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.

          -  Prior screen failure, randomization, participation, or enrollment in this study or
             prior exposure to any exogenous PTH, PTH fragments or analogs 3 months prior to dosing
             with rhPTH(1-84).

          -  Unable to refrain from or anticipates the use of any medication or substance
             (including prescription or over-the-counter, vitamin supplements, natural or herbal
             supplements) Medication, Supplements, and Dietary Products) for the prohibited time
             period.

          -  Has been on a diet incompatible with the study diet or had any substantial changes in
             eating habits, in the opinion of the Investigator or designee, within the 30 days
             prior to the first dosing and throughout the study.

          -  Donation of blood or significant blood loss within 60 days prior to the first dosing.

          -  Plasma donation within 7 days prior to the first dosing.

          -  Participation in another clinical study within 30 days or 5 half-lives of the study
             drug prior to the first dosing. The 30-day window or 5 half-lives will be derived from
             the date of the last blood collection or dosing, whichever is later, in the previous
             study to Day 1 of Treatment Period 1 of the current study.