Study of rhPTH(1-84) in Japanese Healthy Subjects Compared With Matched Caucasian Healthy Adult Subjects

NCT03150108 | Completed Phase 1 Results FDA Drug

• 1 other identifier: SHP634-102
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypoparathyroidism

Outcome Measures

Primary Outcomes (10)

• 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 (%).

  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 Tmax of PTH(1-84)

  Baseline-adjusted time to reach maximum observed drug concentration (Tmax) of PTH(1-84) in plasma was reported.

  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 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 (%).

  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 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 (%).

  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 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 (%).

  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(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 (%).

  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 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 (%).

  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 t1/2 of PTH(1-84) in Plasma

  Baseline-adjusted Terminal Half-life (t1/2) of PTH(1-84) in plasma was reported.

  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 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 (%).

  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 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 (%).

  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

Secondary Outcomes (11)

• 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 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

• 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

• 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)

• 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)

Study Arms (2)

Non-Hispanic Caucasians

EXPERIMENTAL

Subjects will receive single dose of 100 microgram (mcg) rhPTH(1-84) subcutaneous (SC) injection on Day 1.

Drug: rhPTH(1-84)

Participants of Japanese Descent

EXPERIMENTAL

Subjects will receive single dose of 100 mcg rhPTH(1-84) SC injection on Day 1; On days 4 and 7, either 25 mcg or 50 mcg SC injection. A washout period of 73 hours will be maintained between each single doses (100 mcg, 50 mcg and 25 mcg) in a cross-over fashion.

Drug: rhPTH(1-84)

Interventions

rhPTH(1-84) DRUG

25 mcg rhPTH(1-84) SC injection

Participants of Japanese Descent

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.
• 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.

You may not qualify if:

• 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:
• 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).
• 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.
• months - fluoride tablets, oral bisphosphonates, methotrexate, growth hormone, digoxin, raloxifene or similar selective estrogen receptor modulators (SERMs).
• 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.

Sponsors & Collaborators

• Shire: lead

Study Sites (1)

Glendale Adventist Medical Center

Glendale, California, 91206, United States

Location

MeSH Terms

Conditions

Hypoparathyroidism

Condition Hierarchy (Ancestors)

Parathyroid Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

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: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2017
• First Posted: May 12, 2017
• Study Start: May 16, 2017
• Primary Completion: June 26, 2017
• Study Completion: June 26, 2017
• Last Updated: June 8, 2021
• Results First Posted: July 12, 2019

Record last verified: 2021-05

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)