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

NCT05137730 | Completed Phase 1 Results FDA Drug

• 1 other identifier: TAK-834-1001
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (7)

• Part I: Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of rhPTH (1-84)

  AUClast was a measure of the total amount of drug in the plasma from time zero to time of the last measurable concentration.

  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

• Part II: Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of rhPTH (1-84)

  AUClast was a measure of the total amount of drug in the plasma from time zero to time of the last measurable concentration.

  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

• Part I: Area Under the Plasma Concentration- Time Curve From Time Zero to Infinity (AUCinf) of rhPTH(1-84)

  AUCinf was the area under the curve extrapolated to infinity, calculated using the observed value of the last non-zero concentration. AUC was be used as a measure of drug exposure. It was derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.

  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

• Part II: Area Under the Plasma Concentration- Time Curve From Time Zero to Infinity (AUCinf) of rhPTH(1-84)

  AUCinf was the area under the curve extrapolated to infinity, calculated using the observed value of the last non-zero concentration. AUC was be used as a measure of drug exposure. It was derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.

  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

• Part I: Maximum Observed Plasma Concentration (Cmax) of rhPTH(1-84)

  Cmax referred to the maximum (or peak) concentration that a drug achieved in the body after the drug had been administrated.

  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

• Part II: Maximum Observed Plasma Concentration (Cmax) of rhPTH(1-84)

  Cmax referred to the maximum (or peak) concentration that a drug achieved in the body after the drug had been administrated.

  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

• Number of Participants With Clinically Significant Changes in Vital Signs Values

  Vital sign assessments included systolic and diastolic blood pressure, pulse rate and body temperature. Any change in vital signs which are deemed clinically significant by the investigator were reported.

  From start of study drug administration up to Day 34

Secondary Outcomes (3)

• Part I and II: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  From start of study drug administration up to Day 34

• Part I and II: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters Reported as TEAEs

  From start of study drug administration up to Day 34

• Part I and II: Number of Participants With Clinically Significant Changes in Clinical Laboratory Values

  From start of study drug administration up to Day 34

Study Arms (6)

Part I: Sequence AB

EXPERIMENTAL

Participants will receive a single SC injection of 100 microgram (mcg) rhPTH(1-84) (Formulation A) on Day 1 of treatment period 1 followed by 100 mcg rhPTH(1-84) (Formulation B) on Day 1 of treatment period 2. A washout period of 96 hours will be maintained between each treatment period.

Drug: rhPTH(1-84)

Part I: Sequence BA

EXPERIMENTAL

Participants will receive a single SC injection of 100 microgram (mcg) rhPTH(1-84) (Formulation B) on Day 1 of treatment period 1 followed by 100 mcg rhPTH(1-84) (Formulation A) on Day 1 of treatment period 2. A washout period of 96 hours will be maintained between each treatment period.

Drug: rhPTH(1-84)

Part II: Sequence CDEF

EXPERIMENTAL

Participants will receive a single SC injection of 25 mcg (dose C) rhPTH(1-84) on Day 1 of treatment period 1 followed by 50 mcg (dose D) rhPTH(1-84) on Day 1 of treatment period 2 followed by 75 mcg (dose E) rhPTH(1-84) on Day 1 of treatment period 3 followed 200 mcg (dose F) rhPTH(1-84) on Day 1 of treatment period 4. A washout period of 48 hours will be maintained between each treatment period 1,2,3 and 4.

Drug: rhPTH(1-84)

Part II: Sequence DFCE

EXPERIMENTAL

Participants will receive a single SC injection of 50 mcg (dose D) rhPTH(1-84) on Day 1 of treatment period 1 followed by 200 mcg (dose F) rhPTH(1-84) on Day 1 of treatment period 2 followed by 25 mcg (dose C) rhPTH(1-84) on Day 1 of treatment period 3 followed by 75 mcg (dose E) rhPTH(1-84) on Day 1 of treatment period 4. A washout period of 48 hours will be maintained between each treatment period 1,2,3 and 4.

Drug: rhPTH(1-84)

Part II: Sequence ECFD

EXPERIMENTAL

Participants will receive a single SC injection of 75 mcg (dose E) rhPTH(1-84) on Day 1 of treatment period 1 followed by 25 mcg (dose C) rhPTH(1-84) on Day 1 of treatment period 2 followed by 200 mcg (dose F) rhPTH(1-84) on Day 1 of treatment period 3 followed by 50 mcg (dose D) rhPTH(1-84) on Day 1 of treatment period 4. A washout period of 48 hours will be maintained between each treatment period 1,2,3 and 4.

Drug: rhPTH(1-84)

Part II: Sequence FEDC

EXPERIMENTAL

Participants will receive a single SC injection of 200 mcg (dose F) rhPTH(1-84) on Day 1 of treatment period 1 followed by 75 mcg (dose E) rhPTH(1-84) on Day 1 of treatment period 2 followed by 50 mcg (dose D) rhPTH(1-84) on Day 1 of treatment period 3 followed by 25 mcg (dose C) rhPTH(1-84) on Day 1 of treatment period 4. A washout period of 48 hours will be maintained between each treatment period 1,2,3 and 4.

Drug: rhPTH(1-84)

Interventions

rhPTH(1-84) DRUG

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.

Also known as: Recombinant Human Parathyroid Hormone

Part I: Sequence AB; Part I: Sequence BA; Part II: Sequence CDEF; Part II: Sequence DFCE; Part II: Sequence ECFD; Part II: Sequence FEDC

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Takeda: lead
• Takeda Development Center Americas, Inc.: collaborator

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

Related Links

• To obtain more information on the study, click here/on this link

MeSH Terms

Interventions

Parathyroid Hormone

Intervention Hierarchy (Ancestors)

Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2021
• First Posted: November 30, 2021
• Study Start: November 29, 2021
• Primary Completion: April 15, 2022
• Study Completion: April 15, 2022
• Last Updated: December 15, 2023
• Results First Posted: December 15, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: 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.

Locations

US (1)