Clinical trial NCT05137730: 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
Official title: A Randomized, Open-label, Single-center, Single-dose Study to Evaluate the Relative Bioavailability of a New Formulation Compared With the Approved Formulation of Recombinant Human Parathyroid Hormone (rhPTH[1-84]) and to Assess Dose Linearity of the New Formulation in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Takeda Development Center Americas, Inc.
First posted: 2021-11-30
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief 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.

Detailed description: This study will be conducted in two parts (Part I and Part II). Part I consists of two treatment periods with 2 sequences and part II consists of four treatment periods with 4 sequences. In Part I, relative bioavailability of Formulation A (Test: 100 microgram \[mcg\] rhPTH\[1-84\]) will be compared with Formulation B (Reference: 100 mcg rhPTH\[1-84\]). In Part II, dose linearity of the new formulation, Formulation A, of rhPTH (1-84) will be assessed based on 4 different dose levels as dose c - f (dose c = 25 mcg, dose d = 50 mcg, dose e = 75 mcg and f = 200 mcg). Both parts may be conducted concurrently.

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.

Primary outcomes:
measure: Part I: Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of rhPTH (1-84)
timeFrame: Pre-dose, 0.08, 0.16, 0.33, 0.5, 0.75, 1.0, 1.25,1.5,2.0, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours post dose
measure: Part II: Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of rhPTH (1-84)
timeFrame: Pre-dose, 0.08, 0.16, 0.33, 0.5, 0.75, 1.0, 1.25,1.5,2.0, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours post dose
measure: Part I: Area Under the Plasma Concentration- Time Curve From Time Zero to Infinity (AUCinf) of rhPTH(1-84)
timeFrame: Pre-dose, 0.08, 0.16, 0.33, 0.5, 0.75, 1.0, 1.25,1.5,2.0, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours post dose
measure: Part II: Area Under the Plasma Concentration- Time Curve From Time Zero to Infinity (AUCinf) of rhPTH(1-84)
timeFrame: Pre-dose, 0.08, 0.16, 0.33, 0.5, 0.75, 1.0, 1.25,1.5,2.0, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours post dose
measure: Part I: Maximum Observed Plasma Concentration (Cmax) of rhPTH(1-84)
timeFrame: Pre-dose, 0.08, 0.16, 0.33, 0.5, 0.75, 1.0, 1.25,1.5,2.0, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours post dose
measure: Part II: Maximum Observed Plasma Concentration (Cmax) of rhPTH(1-84)
timeFrame: Pre-dose, 0.08, 0.16, 0.33, 0.5, 0.75, 1.0, 1.25,1.5,2.0, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours post dose
measure: Number of Participants With Clinically Significant Changes in Vital Signs Values
timeFrame: From start of study drug administration up to Day 34
Secondary outcomes:
measure: Part I and II: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: From start of study drug administration up to Day 34
measure: Part I and II: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters Reported as TEAEs
timeFrame: From start of study drug administration up to Day 34
measure: Part I and II: Number of Participants With Clinically Significant Changes in Clinical Laboratory Values
timeFrame: From start of study drug administration up to Day 34
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Celerion
state: Arizona
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: